bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparisons of Three Measures of Maternal Engagement Activities in the Neonatal Intensive Care Unit
Authors: Greenfield Jennifer C. , Weikel Blair W. , Bourque Stephanie L. , Hwang Sunah S. , Klawetter Susanne , Roybal Kristi L. , Palau Mauricio A. , Scott Jessica , Shah Pari , Brown Kyria , Neu Madalynn
Published: February 2022

Background

Mothers’ engagement with their hospitalized preterm infant(s) is recognized as an important aspect of treatment in neonatal intensive care units (NICUs). However, no gold standard exists for measuring maternal engagement, and the various methods used to measure mothers’ time have documented limitations.

Objectives

This study sought to compare three measurement methods of maternal engagement (a five-item maternal cross-sectional survey, time use diaries, and electronic health records [EHRs]) to identify whether these methods capture consistent data and patterns in detected differences in measures of engagement.

Methods

Maternal engagement was defined as time spent visiting the infant in the NICU (presence), holding (blanket holding in the mother’s arms or by kangaroo care [KC]), and caregiving (e.g., bathing and changing diapers). The survey estimating daily maternal engagement was administered in two Level III NICUs and one Level IV NICU at study enrollment, at least 2 weeks after admission. Mothers then completed the daily time use diaries until infant discharge. Data were also collected from participants’ EHRs, charted by nursing staff. Wilcoxon signed-rank tests were used for pairwise analysis of the three measures for maternal engagement activities.

Results

A total of 146 participants had data across all three measurement types and were included in the analysis. In the Level III NICUs (n = 101), EHR data showed significantly more time spent with all engagement activities than the diary data. In the Level IV data, only differences in time holding were significant when comparing EHR data with survey data, with mothers reporting more time doing KC and less time blanket holding. Comparison of EHR data with diary data showed more time in all activities except KC.

Discussion

In most cases, time spent in engagement activities measured in the EHR was higher than in the surveys or time use diaries. Accuracy of measurements could not be determined because of limitations in data collection, and there is no gold standard for comparison. Nevertheless, findings contribute to ongoing efforts to develop the most valuable and accurate strategies for measuring maternal engagement—a significant predictor of maternal and infant health.
Tripartite Analysis
Authors: Younas Ahtisham , Sundus Amara
Published: February 2022

Background

Effective data integration is a daunting task in mixed methods research. Several frameworks for data integration exist, but the choice of and the technique for integration depend upon the research question and design. Innovative integration techniques continuously need to be developed to tackle the integration challenge and provide alternative ways for researchers to generate plausible mixed meta-inferences.

Objectives

The purpose of this study was to describe a new data analysis technique, tripartite analysis (TriPA), and illustrate its use in a convergent mixed-methods study.

Methods

This technique was developed based on a convergent mixed-methods study underpinned by dialectical pluralism aimed to understand Pakistani nursing students’ perspectives about compassion and compassionate care and how these perspectives are consistent with the conceptualizations of compassion in nursing literature.

Results

TriPA entails analysis and integration using joint displays at three levels: case-by-case integrated analysis, separate and then merged quantitative and qualitative analysis, and comparative and integrated analysis of Levels I and II findings.

Discussion

TriPA can enable researchers to develop a more nuanced understanding of a given phenomenon through integration at various levels by identifying linkages within cases and across the whole data set and recognizing relational connections and emerging patterns.
Sleep Characteristics, Mood, Somatic Symptoms, and Self-Care Among People With Heart Failure and Insomnia
Authors: Breazeale Stephen , Jeon Sangchoon , Hwang Youri , O’Connell Meghan , Nwanaji-Enwerem Uzoji , Linsky Sarah , Yaggi H. Klar , Jacoby Daniel L. , Conley Samantha , Redeker Nancy S.
Published: February 2022

Background

Almost 50% of people with heart failure (HF) experience chronic insomnia and must perform self-care to manage their day-to-day healthcare needs. Understanding multifactorial influences on self-care, including demographic, clinical, and sleep characteristics, and mood and somatic symptoms will help identify people at highest risk for poor self-care. However, past research focused only on the associations of single symptoms and self-care. Multivariate approaches are needed to account for the synergistic associations of self-care with sleep, mood, and somatic symptoms among people with HF.

Objectives

The aims of the study were to (a) evaluate the levels of self-care maintenance and self-care confidence among people with stable HF and chronic insomnia; (b) identify the clinical and demographic correlates of self-care maintenance and confidence among people with stable HF and chronic insomnia; and (c) identify the associations between sleep characteristics, mood and somatic symptoms, and self-care maintenance and confidence among people with stable HF and chronic insomnia.

Methods

We utilized a cross-sectional design with 195 adult participants who had chronic HF and insomnia. We assessed for symptoms of anxiety; depression; dyspnea; fatigue; stress; insomnia severity; and sleep disturbance, impairment, and quality. Self-care was measured using the Self-Care for Heart Failure Index v6.2. We used generalized linear models to test the associations between the demographic and clinical factors and self-care maintenance and confidence; exploratory and confirmatory factor analysis to identify the factor structure underlying the symptoms; and structural equation modeling to test the combined associations of the demographic and clinical factors and latent factors with self-care maintenance and confidence.

Results

Self-care maintenance, confidence, and management were inadequate in most participants. We identified three latent factors among the nine symptoms: “sleep characteristics,” “mood,” and “somatic symptoms.” In the structural equation model, “sleep characteristics,” White race, and having a left ventricular ejection fraction of <45 were associated with self-care maintenance. Age was negatively associated with self-care confidence.

Discussion

Poor sleep characteristics negatively influence the ability of people with HF and insomnia to perform self-care behaviors. Knowledge of the associations among age, left ventricular ejection fraction, and race with self-care will help clinicians and future researchers identify those at risk for poor self-care.
Clinical Report: Experiences of a Driver with Vision Impairment when Using a Tesla Car
Authors: Xu Jing , Kendrick Karen , Bowers Alex R.
Published: February 2022

SIGNIFICANCE

Assisted and autonomous driving technologies may be a new paradigm shift for the driving rehabilitation field to enable less restricted driving, increase driving confidence, and maintain driving safety for drivers with vision impairment.

PURPOSE

This study aimed to document how a driver with vision impairment uses assistance and automation systems in a Tesla car based on real-world experiences of using these technologies.

METHODS

A 53-year-old man with Stargardt disease and 20/182 visual acuity self-explored the use of driver assistance technologies, which resulted in purchasing a Tesla Model Y with the full self-driving package in 2020. Two semistructured interviews were administered to quantify the driver's driving habits, adaptive strategies, use of the assisted and semiautonomous driving features in the Tesla car, and use of his bioptic telescope.

RESULTS

When driving a Tesla car, the patient developed new driving strategies by codriving with different assisted and semiautonomous functions (e.g., Traffic-Aware Cruise Control, Traffic Light and Stop Sign Control, Autopilot) in different road environments. He shifted his main task from active driving to supervising the car automation systems in most driving situations. He also integrated a new use of his bioptic telescope to support him with monitoring the road environment before granting permission to the automated systems for car maneuver changes. The patient reported that driving confidence greatly increased and that he is able to drive more often and in situations that he would otherwise avoid because of difficulties related to his vision.

CONCLUSIONS

This clinical report demonstrates how assisted and semiautonomous driving systems in a Tesla car were used to support daily driving by a driver with vision impairment. Codriving with these systems allows him to confidently drive more often and to avoid less situations than he used to.
Monocular Perception of Equidistance: The Effects of Viewing Experience and Motion-generated Information
Authors: Chen Shenying , Li Yusi , Pan Jing Samantha
Published: February 2022

SIGNIFICANCE

Using static depth information, normal observers monocularly perceived equidistance with high accuracy. With dynamic depth information and/or monocular viewing experience, they perceived with high precision. Therefore, monocular patients, who were adapted to monocular viewing, should be able to perceive equidistance and perform related tasks.

PURPOSE

This study investigated whether normal observers could accurately and precisely perceive equidistance with one eye, in different viewing environments, with various optical information and monocular viewing experience.

METHODS

Sixteen normally sighted observers monocularly perceived the distance (5 to 30 m) between a target and the self and replicated it either in some hallways that contained ample static monocular depth information but had a limited field of view or on a lawn that contained less depth information but had a large field of view. Participants remained stationary or walked 5 m before performing the task, as a manipulation of the availability of dynamic depth information. Eight observers wore eye patches for 3 hours before the experiment and gained monocular viewing experience, whereas the others did not. Both accuracy and precision were measured.

RESULTS

As long as static monocular depth information was available, equidistance perception was effectively accurate, despite minute underestimation. Perception precision was improved by prior monocular walking and/or experience with monocularity. Accuracy and precision were not affected by the viewing environments.

CONCLUSIONS

Using static and dynamic monocular depth information and/or with monocular experience, normal observers judged equidistance with reliable accuracy and precision. This implied that patients with monocular vision, who are better adapted than participants of this study, should also be able to perceive equidistance and perform distance-dependent tasks in natural viewing environments.
Case Series: Underdiagnosis of Ocular and Oculocutaneous Rosacea in an African American Pediatric Population
Authors: Bass Olivia , Crane Danielle
Published: February 2022

SIGNIFICANCE

As the global multiracial population grows, this case series highlights the current underdiagnosis and misdiagnosis of ocular and oculocutaneous rosacea and the importance of properly identifying the condition in a darkly pigmented pediatric population.

PURPOSE

This series aims to report the clinical presentation of ocular and oculocutaneous rosacea and adverse sequelae of misdiagnosis in two pediatric African American patients.

CASE REPORT

One 11-year-old boy and one 10-year-old girl, both darkly pigmented African American patients, presented with a history of chronic ocular irritation. The male patient was seen by an eye care provider eight times over the past 7 years for recurrent anterior ocular inflammation. The female patient presented to the clinic with chronic anterior segment ocular inflammation for 1 year. Both patients were previously treated for their acute signs and symptoms. The male patient was diagnosed with ocular rosacea, and the female patient was diagnosed with oculocutaneous rosacea. Both patients were subsequently treated for their underlying inflammatory condition, yielding an improvement in their ocular health.

CONCLUSIONS

These two cases bring attention to the underdiagnosis and misdiagnosis of ocular and oculocutaneous rosacea in pediatric patients with darkly pigmented skin. Timely and accurate diagnosis is critical to minimize the risk of significant visual and dermatological sequelae.
Pediatric Urgent Care Center Management of Traumatic Injuries in Infants and Children
Authors: Chardavoyne Paige C. , Montgomery Emily J. , Montalbano Amanda , Olympia Robert P.
Published: February 2022

Objectives

To determine pediatric urgent care (PUC) clinician adherence to evidence-based practice guidelines in the management of pediatric trauma and to evaluate PUC emergency preparedness for conditions such as severe hemorrhage.

Methods

A questionnaire covering acute management of 15 pediatric traumatic injuries, awareness of the Stop the Bleed initiative, and presence of emergency equipment and medications was electronically distributed to members of the Society for Pediatric Urgent Care. Clinician management decisions were evaluated against evidence-based practice guidelines.

Results

Eighty-three completed questionnaires were returned (25% response rate). Fifty-three physician and 25 advanced practice provider (APP) questionnaires were analyzed. Most respondents were adherent to evidence-based practice guidelines in the following scenarios: cervical spine injury; head injury without neurologic symptoms; blunt abdominal injury; laceration without bleeding, foreign body, or signs of infection; first-degree burn; second-degree burn with less than 10% total body surface area; animal bite with and without probable tenosynovitis; and orthopedic fractures. Fever respondents were adherent in the following scenarios: head injury with altered mental status (adherence: physicians, 64%; APPs, 44%) and laceration with foreign body and persistent hemorrhage (adherence: physicians, 52%; APPs, 41%). Most respondents (56%) were unaware of Stop the Bleed and only 48% reported having a bleeding control kit/tourniquet at their urgent care.

Conclusions

Providers in our sample demonstrated adherence with pediatric trauma evidence-based practice guidelines. Increased PUC provider trauma care certification, PUC incorporation of Stop the Bleed education, and PUC presence of equipment and medications would further improve emergency preparedness.
Serous Tubal Intraepithelial Carcinoma in a Risk-reducing Salpingo-oophorectomy Specimen From a RAD51D Mutation Carrier: A Case Report
Authors: Gregory-Davis Kalin J. , Walker Allison , Colello Laura S. , McKinnon Wendy , Everett Elise , Chang Martin C.
Published: February 2022

The RAD51D gene codes a protein-paralog of the RAD51 DNA recombinase, which catalyzes DNA strand exchange during homologous recombination. Similar to BRCA1/BRCA2, mutations in RAD51D both predispose to ovarian carcinoma and impart sensitivity to poly (ADP-ribose) polymerase inhibitors in preclinical studies. Based on cancer risk prediction models, RAD51D mutations pose a moderate-to-high risk for ovarian cancer warranting consideration for risk-reducing surgery. We report a case of serous tubal intraepithelial carcinoma in a patient undergoing risk-reducing total hysterectomy with bilateral salpingo-oophorectomy for a RAD51D pathogenic variant. The histopathologic and p53-immunophenotypic features of this lesion are similar to those reported previously in BRCA1/BRCA2 mutation carriers and those of serous tubal intraepithelial carcinoma associated with sporadic high-grade serous carcinomas. These features include marked increase in nuclear-to-cytoplasmic ratio, loss of cell polarity, absence of ciliation, prominent nucleoli, mitotic activity, epithelial stratification, surface exfoliative changes, and complete loss of p53 staining. Although familial ovarian cancers with mutations in RAD51D—or other genes in the Fanconi anemia pathway—are much less common those with BRCA1/BRCA2 mutations, our findings support a common phenotype for early serous cancers in this pathway.
T-Cadherin, E-Cadherin, PR-A, and ER-α Levels in Deep Infiltrating Endometriosis
Authors: Kalkan Uzeyir , Biyik Ismail , Simsek Sercan
Published: February 2022

The goal of this study was to compare the T-cadherin, E-cadherin, progesterone receptor (PR), and estrogen receptor (ER) staining levels of deep infiltrating endometriosis (DIE) tissue, ovarian endometriomas and normal endometrial tissues in the same individuals. The tissue sections of both DIE nodule(s) and endometrioma(s) of 15 cases were examined. As a control group, normal endometrial tissue sections of 23 cases were examined. T-cadherin, E-cadherin, ER-α, and PR-A staining levels of DIE, endometrioma tissues, and endometrial tissues were compared immunohistochemically. H-score was calculated to compare the expression of T-cadherin, E-cadherin, ER-α, and PR-A in immunohistochemical staining based on the percentage of cells stained at each intensity level. T-cadherin, E-cadherin, ER, and PR H-score were lowest in DIE tissue and highest in endometrial tissue (P<0.0001, <0.0001, <0.0001, and <0.0001, respectively). In correlation analysis, a positive correlation was found between T-cadherin, E-cadherin, PR, and ER H-score (P<0.0001 for each). T-cadherin, E-cadherin, ER, and PR H-score were lowest in DIE tissue and highest in endometrium tissue. We think that examination of DIE tissue and endometrioma tissue from the same individual excludes the possibility of an effect due to different genetic and environmental factors from different individuals. With the help of this exclusion we showed that DIE and endometrioma have different biological properties.
Unusual Ovarian Tumors With Endometrioid Proliferations Co-Expressing Estrogen Receptor and CDX-2 Arising in Cystadenofibromatous Background: Report of 3 Cases
Authors: McMullen-Tabry Emily R. , Sciallis Andrew P. , Udager Aaron M. , Skala Stephanie L.
Published: February 2022

This report describes 3 cases of ovarian tumors with unusual glandular proliferations co-expressing estrogen receptor and CDX-2 by immunohistochemistry set in cystadenofibromatous background. Targeted next-generation sequencing was performed on the cyst lining epithelium and glandular proliferations for all cases; CTNNB1 mutations were detected in the glandular proliferations of all neoplasms. The cyst lining of case 1 demonstrated a different CTNNB1 mutation from the matched glandular proliferation. No mutations were detected in the cyst lining from case 2. The cyst lining and glandular proliferation for case 3 harbored identical ATM and PIK3CA mutations with an additional CTNNB1 mutation in the glandular proliferation. To our knowledge, this is the first reported series of endometrioid proliferations with co-expression of estrogen receptor and CDX-2 in cystadenofibromatous background.
Promoting Acceptance and Adherence to Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial
Authors: Volpato Eleonora , Banfi Paolo , Pagnini Francesco
Published: February 2022

Objective

People with chronic obstructive pulmonary disease (COPD) may suffer from anxiety, depression, low quality of life, and cognitive deficits that could play a role in their clinical conditions. These situations could be worsened during the adaptation process to a new treatment such as noninvasive ventilation (NIV), which is often rejected or inappropriately used. The study aimed to analyze the impact of a brief psychological support intervention on adherence to NIV among patients with COPD.

Methods

A two-branch randomized controlled trial was conducted on 90 patients with COPD who had an indication for NIV. The experimental group received cognitive behavioral therapy support, including counseling, relaxation, and mindfulness-based exercises. Controls received standard care and watched educational videos. The course had been structured for four to eight meetings at the hospital, at home, and/or via telemedicine.

Results

The psychological intervention was related to improvements in both adherence to NIV (F(304) = 19.054, p < .001) and quality of life (F(156) = 10.264, p = .002) after eight meetings from baseline compared with the control group. Results indicated a significant change in the quality of life also over time (F(71.480) = 8.114, p = .006).

Conclusions

The findings suggest that the psychological intervention is an appropriate treatment for acceptance of and adherence to NIV in COPD in clinical practice and highlight the importance of determining the underlying reasons for NIV use.

Trial Registration:
ClinicalTrials.gov identifier NCT02499653.
First whole-genome sequence of Cervid atadenovirus A outside of the United States from an Adenoviral hemorrhagic disease epizootic of black-tailed deer in Canada
Authors: Lung Oliver , Fisher Mathew , Nebroski Michelle , McGregor Glenna , Schwantje Helen , Joseph Tomy
Published: February 2022

A complete 30,616 nucleotide Cervid atadenovirus A genome was determined from tissues of a black-tailed deer that died in 2020 in British Columbia, Canada. Unique, non-synonymous SNPs in the E1B, Iva2 and E4.3 coding regions, and deletions totalling 74 nucleotides not observed in moose and red deer isolates were present.
Having the ‘right’ microbiome matters for host trait expression and the strength of mutualism between duckweeds and microbes
Authors: O’Brien Anna M. , Laurich Jason , Frederickson Megan E.
Published: February 2022

An organism’s phenotypes and fitness often depend on interactive effects of its genome (Ghost), microbiome (Gmicrobe), and environment (E). These G xG, G xE, and G xG xE effects fundamentally shape host-microbiome (co)evolution and may be widespread, but are rarely compared within a single experiment. We collected and cultured Lemna minor (duckweed) and its associated microbiome from 10 sites across an urban-to-rural ecotone. We factorially manipulated host genotype and microbiome in two environments (low and high zinc, an urban aquatic stressor) in an experiment with 200 treatments: 10 host genotypes × 10 microbiomes × 2 environments. Host genotype explained the most variation in L. minor fitness and traits, while microbiome effects depended on host genotype (G xG) or environment (G xE). Hosts had higher fitness and microbes grew fastest when tested microbiomes more closely matched field microbiomes, suggesting some local adaptation between hosts and their microbiota. High microbiome similarity also led to more predictable host trait expression. In contrast, although zinc decreased host fitness, we observed no local adaptation of urban duckweed or microbes to high-zinc conditions. Thus, we found that host fitness and trait expression are contingent on microbiome composition, with implications for microbiome engineering and host-microbiome evolution.
Increased prevalence of a frontoparietal brain state is associated with better motor recovery after stroke affecting dominant-hand corticospinal tract
Authors: Olafson Emily , Russello Georgia , Jamison Keith W , Liu Hesheng , Wang Danhong , Bruss Joel E , Boes Aaron D , Kuceyeski Amy
Published: February 2022

Strokes cause lesions that damage brain tissue, disrupt normal brain activity patterns and can lead to impairments in motor function. Although modulation of cortical activity is central to stimulation-based rehabilitative therapies, aberrant and adaptive patterns of brain activity after stroke have not yet been fully characterized. Here, we apply a brain dynamics analysis approach to study longitudinal brain activity patterns in individuals with ischemic pontine stroke. We first found 4 commonly occurring brain states largely characterized by high amplitude activations in the visual, frontoparietal, default mode, and motor networks. Stroke subjects spent less time in the frontoparietal state compared to controls. For individuals with dominant-hand CST damage, more time spent in the frontoparietal state from 1 week to 3-6 months post-stroke was associated with better motor recovery over the same time period, an association which was independent of baseline impairment. Furthermore, the amount of time spent in brain states was linked empirically to functional connectivity. This work suggests that when the dominant-hand CST is compromised in stroke, resting state configurations may include increased activation of the frontoparietal network, which may facilitate compensatory neural pathways that support recovery of motor function when traditional motor circuits of the dominant-hemisphere are compromised.
Genetic and microbial diversity of the invasive mosquito vector speciesCulex tritaeniorhynchusacross its extensive inter-continental geographic range
Authors: Jeffries Claire L. , Tantely Luciano M. , Kadriaj Perparim , Blagrove Marcus S. C. , Lytra Ioanna , Orsborne James , Al-Amin Hasan M. , Mohammed Abdul Rahim , Alam Mohammad Shafiul , Girod Romain , Afrane Yaw A. , Bino Silvia , Robert Vincent , Boyer Sebastien , Baylis Matthew , Velo Enkelejda , Hughes Grant L. , Walker Thomas
Published: February 2022

Culex (Cx.) tritaeniorhynchusis a mosquito species with an extensive and expanding inter-continental geographic distribution, currently reported in over 50 countries, across Asia, Africa, the Middle East, Europe and now Australia. It is an important vector of medical and veterinary concern, capable of transmitting multiple arboviruses which cause significant morbidity and mortality in human and animal populations. In regions endemic for Japanese encephalitis virus (JEV) in Asia,Cx. tritaeniorhynchusis considered the major vector and this species has also been shown to contribute to the transmission of several other significant zoonotic arboviruses, including Rift Valley fever virus and West Nile virus.

Significant variation in vectorial capacity can occur between different vector populations. Obtaining knowledge of a species from across its geographic range is crucial to understanding its significance for pathogen transmission across diverse environments and localities. Vectorial capacity can be influenced by factors including the mosquito genetic background, composition of the microbiota associated with the mosquito and the co-infection of human or animal pathogens. In addition to enhancing information on vector surveillance and potential risks for pathogen transmission, determining the genetic and microbial diversity of distinct populations of a vector species is also critical for the development and application of effective control strategies.

In this study, multiple geographically dispersed populations ofCx. tritaeniorhynchusfrom countries within Europe, Africa, Eurasia and Asia were sampled. Molecular analysis demonstrated a high level of genetic and microbial diversity within and between populations, including genetic divergence in the mosquitoCO1gene, as well as diverse microbiomes identified by16S rRNAgene amplicon sequencing. Evidence for the detection of the endosymbiotic bacteriaWolbachiain some populations was confirmed usingWolbachia-specific PCR detection and sequencing ofWolbachiaMLST genes; in addition to PCR-based detection of insect-specific viruses. Laboratory vector competence showedCx. tritaeniorhynchusfrom a Greek population are likely to be competent vectors of JEV. This study expands understanding of the diversity ofCx. tritaeniorhynchusacross its inter-continental range, highlights the need for a greater focus on this invasive vector species and helps to inform potential future directions for development of vector control strategies.
Multi-ancestry fine-mapping improves precision to identify causal genes in transcriptome-wide association studies
Authors: Lu Zeyun , Gopalan Shyamalika , Yuan Dong , Conti David V. , Pasaniuc Bogdan , Gusev Alexander , Mancuso Nicholas
Published: February 2022

Transcriptome-wide association studies (TWAS) are a powerful approach to identify genes whose expression associates with complex disease risk. However, non-causal genes can exhibit association signals due to confounding by linkage disequilibrium patterns (LD) and eQTL pleiotropy at genomic risk regions which necessitates fine-mapping of TWAS signals. Here, we present MA-FOCUS, a multi-ancestry framework for the improved identification of genes underlying traits of interest. We demonstrate that by leveraging differences in ancestry-specific patterns of LD and eQTL signals, MA-FOCUS consistently outperforms single-ancestry fine-mapping approaches with equivalent total sample size across multiple metrics. We perform 15 blood trait TWAS using genome-wide summary statistics (average NEA=511k, NAA=13k) and lymphoblastoid cell line eQTL data from cohorts of primarily European and African continental ancestries. We recapitulate evidence demonstrating shared genetic architectures for eQTL and blood traits between the two ancestry groups and observe that gene-level effects correlate 20% more strongly across ancestries compared with SNP-level effects. We perform fine-mapping using MA-FOCUS and find evidence that genes at TWAS risk regions are more likely to be shared across ancestries rather than ancestry-specific. Using multiple lines of evidence to validate our findings, we find gene sets produced by MA-FOCUS are more enriched in hematopoietic categories compared to alternative approaches (P = 1.73 × 10−16). Our work demonstrates that including, and appropriately accounting for, genetic diversity can drive deeper insights into the genetic architecture of complex traits.
Conceptual and analytical approaches for modeling the developmental origins of inequality
Authors: Malani Anup , Archie Elizabeth A. , Rosenbaum Stacy
Published: February 2022

In many species, individuals who experience harsh conditions during development often have poor health and fitness outcomes in adulthood relative to peers who do not. There are two classes of evolutionary hypotheses for the origins of these early life contributors to inequality in adulthood: developmental constraints (DC) models, which focus on the deleterious effects of low-quality early-life environments, and predictive adaptive response (PAR) hypotheses, which emphasize the cost of mismatches between early and adult environments. Distinguishing DC and PAR models empirically is difficult for both conceptual and analytical reasons. Here, we resolve this difficulty by providing explicit mathematical definitions for DC, PARs, and related concepts, and propose a novel, quadratic regression-based statistical test derived from these definitions. Simulations show that this approach improves the ability to discriminate between DC and PAR hypotheses relative to a common alternative based on testing for interaction effects between developmental and adult environments. Simulated data indicate that the interaction effects approach often conflates PARs with DC, while the quadratic regression approach yields high sensitivity and specificity for detecting PARs. Our results highlight the value of linking verbal and visual models to a formal mathematical treatment for understanding the developmental origins of inequitable adult outcomes.
Operational tolerance is early acquired and long maintained in 50% liver allograft transplantation
Authors: Chen Guoyong , Tang Gaofeng , Zhao Huibo , Wei Sidong , Guo Xiaoyan , Liu Fangzhou , Lu Di , Guo Hui , Zhou Shaotang
Published: February 2022

Lifelong anti-rejection therapy is mandatory to weaken the host immune system and maintain the graft functions after organ transplantation, its toxicities and side-effects incidentally elicit mortalities and morbidities. Operational tolerance is a long immunosuppression-free state in which the allograft functions well and no immunological rejections occur, and no operational tolerance is clinically in use. Here we introduce that operational tolerance, based on hypertrophy to hyperplasia switch upon liver regeneration, is early achieved and maintained well in half-size liver allograft transplantation through host bone marrow stem cells repopulation and 9-day immunosuppression. Compared with whole and partial rat liver transplantations as the controls, longer-term survivals (over 430 days) were observed in the tolerant hosts (p= 0.001), the allografts functioned well and no acute or chronic rejections were confirmed by histology examinations. Further study revealed that the allograft was reinstituted by host-derived stem cells marked with CD34, which migrated, repopulated and differentiated after mobilization. However donor-specific hyporesponse was not achieved through skin transplantation, indicating no adaptive immune activity occurrence. Our protocol is characteristic of targeting the allografts and almost no immunological intervention, offering a novel avenue to operational tolerance induction which is of highly clinical relevance.
“polishCLR: a Nextflow workflow for polishing PacBio CLR genome assemblies”
Authors: Chang Jennifer , Stahlke Amanda R. , Chudalayandi Sivanandan , Rosen Benjamin D. , Childers Anna K. , Severin Andrew
Published: February 2022

Long-read sequencing has revolutionized genome assembly, yielding highly contiguous, chromosome-level contigs. However, assemblies from some third generation long read technologies, such as Pacific Biosciences (PacBio) Continuous Long Reads (CLR), have a high error rate. Such errors can be corrected with short reads through a process called polishing. Although best practices for polishing non-model de novo genome assemblies were recently described by the Vertebrate Genome Project (VGP) Assembly community, there is a need for a publicly available, reproducible workflow that can be easily implemented and run on a conventional high performance computing environment. Here, we describe polishCLR (https://github.com/isugifNF/polishCLR), a reproducible Nextflow workflow that implements best practices for polishing assemblies made from CLR data. PolishCLR can be initiated from several input options that extend best practices to suboptimal cases. It also provides re-entry points throughout several key processes including identifying duplicate haplotypes in purge_dups, allowing a break for scaffolding if data are available, and throughout multiple rounds of polishing and evaluation with Arrow and FreeBayes. PolishCLR is containerized and publicly available for the greater assembly community as a tool to complete assemblies from existing, error-prone long-read data.
Compartmental Neuropeptide Release Measured Using a New Oxytocin Sensor
Authors: Qian Tongrui , Wang Huan , Wang Peng , Geng Lan , Mei Long , Osakada Takuya , Tang Yan , Kania Alan , Grinevich Valery , Stoop Ron , Lin Dayu , Luo Minmin , Li Yulong
Published: February 2022

As a peptide hormone and neuromodulator, oxytocin (OT) plays a critical role in a variety of physiological and pathophysiological processes in both the central nervous system and the periphery. However, the processes that regulate spatial OT release in the brain remain enigmatic. Here, we developed a genetically encoded GPCR activation-based (GRAB) OT sensor called GRABOT1.0. Using this sensor, we directly visualized stimulation-induced OT release from specific compartments of OT neurons in acute brain slices, and discovered that N-type calcium channels predominantly mediate axonal OT release, while L-type calcium channels mediate somatodendritic OT release. In addition, we found that components in the fusion machinery of OT release differ between axon terminals versus somata and dendrites. Finally, we demonstrated the sensor responses to the activation of OT neurons in various brain regions in vivo and revealed region specific OT release during male courtship behavior. Taken together, these results provide key insights regarding the role of compartmental OT release in the control of physiological and behavioral functions.
Microbial turnover and dispersal events occur in sync with plant phenology in the perennial evergreen tree crop, Citrus sinensis
Authors: Ginnan Nichole A. , De Anda N. Itzel , Freitas Vieira Flavia Campos , Rolshausen Philippe , Roper M. Caroline
Published: February 2022

Emerging research indicates that plant-associated microbes can alter plant developmental timing. However, it is unclear if host phenology impacts microbial community assembly. Microbiome studies in annuals or deciduous perennial plants face challenges in separating effects of tissue age from phenological driven effects on the microbiome. In contrast, evergreen perennial trees, like Citrus sinensis, retain leaves for years allowing for uniform sampling of similarly aged leaves from the same developmental cohort. This aids in separating phenological effects on the microbiome from impacts due to annual leaf maturation/senescence. Here we used this system to test the hypothesis that host phenology acts as a driver of microbiome composition. Citrus sinensis leaves and roots were sampled during seven phenological stages. Using amplicon-based sequencing, followed by diversity, phylogenetic, differential abundance, and network analyses we examined changes in bacterial and fungal communities. Host phenological stage is the main determinant of microbiome composition, particularly within the foliar bacteriome. Microbial enrichment/depletion patterns suggest that microbial turnover and dispersal were driving these shifts. Moreover, a subset of community shifts were phylogenetically conserved across bacterial clades suggesting that inherited traits contribute to microbe-microbe and/or plant-microbe interactions during specific phenophases. Plant phenology influences microbial community composition. These findings enhance understanding of microbiome assembly and identify microbes that potentially influence plant development and reproduction.
Allele Dispersion Score: Quantifying the range of allele frequencies across populations, based on UMAP
Authors: Correard Solenne , Arbour Laura , Wasserman Wyeth W.
Published: February 2022

Genomic variation plays a crucial role in biology, serving as a base for evolution - allowing for adaptation on a species or population level. At the individual level, however, specific alleles can be implicated in diseases. To interpret genetic variants identified in an individual potentially affected with a rare genetic disease, it is fundamental to know the population frequency of each allele, ideally in an ancestry matched cohort. Equity in human genomics remains a challenge for the field, and there are not yet cohorts representing most populations. Currently, when ancestry matched cohorts are not available, pooled variant libraries are used, such as gnomAD, the Human Genome Diversity Project (HGDP) or the 1,000 Genomes Project (now known as IGSR: International Genome Sample Resource). When working with a pooled collection of variant frequencies, one of the challenges is to determine efficiently if a variant is broadly spread across populations or appears selectively in one or more populations. While this can be accomplished by reviewing tables of population frequencies, it can be advantageous to have a single score that summarizes the observed dispersion. This score would not require classifying individuals into populations, which can be complicated if it is a homogenous population, or can leave individuals excluded from all the predefined population groups. Moreover, a score would not display fine-scaled population information, which could have privacy implications and consequently be inappropriate to release. Therefore, we sought to develop a scoring method based on a Uniform Manifold Approximation and Projection (UMAP) where, for each allele, the score can range from 0 (the variant is limited to a subset of close individuals within the whole cohort) to 1 (the variant is spread among the individuals represented in the cohort). We call this score the Allele Dispersion Score (ADS). The scoring system was implemented on the IGSR dataset, and compared to the current method consisting in displaying variant frequencies for several populations in a table. The ADS correlates with the population frequencies, without requiring grouping of individuals.
Suspicions of two bridgehead invasions ofXylella fastidiosasubsp.multiplexin France
Authors: Dupas Enora , Durand Karine , Rieux Adrien , Briand Martial , Pruvost Olivier , Cunty Amandine , Denancé Nicolas , Donnadieu Cécile , Legendre Bruno , Lopez-Roques Céline , Cesbron Sophie , Ravigné Virginie , Jacques Marie-Agnès
Published: February 2022

Of American origin, a wide diversity ofXylella fastidiosastrains belonging to different subspecies have been reported in Europe since 2013 and its discovery in Italian olive groves. Strains from the subspeciesmultiplex(ST6 and ST7) were first identified in France in 2015 in urban and natural areas. To trace back the most probable scenario of introduction in France, the molecular evolution rate of this subspecies was estimated at 3.2165 × 10-7substitutions per site per year, based on heterochronous genome sequences collected worldwide. This rate allowed the dating of the divergence between French and American strains in 1987 for ST6 and in 1971 for ST7. The development of a new VNTR-13 scheme allowed tracing the spread of the bacterium in France, hypothesizing an American origin. Our results suggest that both sequence types were initially introduced and spread in Provence-Alpes-Côte d’Azur (PACA); then they were introduced in Corsica in two waves from the PACA bridgehead populations.
STAT3gain-of-function mutations connect leukemia with autoimmune disease by pathological dysregulation of NKG2DhiCD8 killer T cells
Authors: Masle-Farquhar Etienne , Jackson Katherine J.L. , Peters Timothy J. , Al-Eryani Ghamdan , Singh Mandeep , Payne Kathryn J. , Rao Geetha , Apps Gabrielle , Kingham Jennifer , Jara Christopher J. , Skvortsova Ksenia , Swarbrick Alexander , Ma Cindy S. , Suan Daniel , Uzel Gulbu , Chua Ignatius , Leiding Jennifer W. , Heiskanen Kaarina , Preece Kahn , Kainulainen Leena , O’Sullivan Michael , Cooper Megan A. , Seppänen Mikko R.J. , Mustjoki Satu , Brothers Shannon , Vogel Tiphanie P. , Brink Robert , Tangye Stuart G. , Reed Joanne H. , Goodnow Christopher C.
Published: February 2022

The association between cancer and autoimmune disease is unexplained, exemplified by T-cell large granular lymphocytic leukemia (T-LGL) where gain-of-function somatic mutations inSTAT3correlate with co-existing autoimmunity. To resolve whether these mutations are the cause or consequence of CD8 clonal expansions and autoimmunity, here we analyse patients with germlineSTAT3GOF syndrome and mice with the T-LGL mutationSTAT3K658Nor the most common germline mutation,STAT3T716M. STAT3 GOF mutations drove accumulation of effector CD8 T cell clones highly expressing the NKG2D receptor for MHC-I-related molecules expressed on stressed cells, and the genes for inflammatory/cytotoxic granzymes, perforin, interferon-γ andCcl5/Rantes. CD8 cells were essential to lethal disease inStat3K658Nmice and their accumulation required NKG2D and the receptor for IL-15 and IL-2, IL2RB. These results demonstrate thatSTAT3GOF mutations cause effector CD8 T cell oligoclonal accumulation and that these rogue T cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.

IN BRIEF

Leukemia and autoimmune-associatedSTAT3gain-of-function mutations dysregulate CD8 T cells to cause autoimmune pathology and oligoclonal expansion of cytotoxic killer CD8 T cells, that depend upon NKG2D and IL2RB receptors for signals displayed on stressed, damaged, infected, or mutated tissues.
Autophagy regulates neuronal excitability by controlling cAMP/Protein Kinase A signaling
Authors: Overhoff M. , Tellkamp F. , Hess S. , Tutas J. , Tolve M. , Faerfers M. , Ickert L. , Mohammadi M. , De Bruyckere E. , Kallergi E. , Dell Vedove A. , Nikoletopoulou V. , Wirth B. , Isensee J. , Hucho T. , Puchkov D. , Isbrandt D. , Krüger M. , Kloppenburg P. , Kononenko N.L.
Published: February 2022

Autophagy provides nutrients during starvation and eliminates detrimental cellular components. However, accumulating evidence indicates that autophagy is not merely a housekeeping process. Here, we show that the protein AuTophaGy 5 (ATG5) functions in neurons to regulate the cAMP-dependent protein kinase A (PKA)-mediated phosphorylation of a synapse-confined proteome. This function of ATG5 is independent of bulk turnover of synaptic proteins and requires the targeting of PKA inhibitory R1 subunits to autophagosomes. Neuronal loss of ATG5 causes synaptic accumulation of PKA R1, which sequesters the PKA catalytic subunit and diminishes the cAMP/PKA-dependent phosphorylation of postsynaptic cytoskeletal proteins mediating AMPAR trafficking. Glutamatergic neurons-confined ATG5 deletion augments AMPAR-dependent excitatory neurotransmission and causes the appearance of spontaneous recurrent seizures in mice. Our findings identify a novel role of autophagy in regulating PKA signaling at glutamatergic synapses and suggest the PKA as a target for restoration of synaptic function in neurodegenerative conditions with autophagy dysfunction.
Comparative genomics of Staphylococcus capitis reveals determinants of speciation
Authors: Chong Charlotte E. , Bengtsson Rebecca J. , Horsburgh Malcolm J.
Published: February 2022

Staphylococcus capitis is primarily described as a human skin commensal but is now emergent as an opportunistic pathogen isolated from bloodstream and prosthetic joint infections, and neonatal intensive care unit (NICU) associated sepsis. We used comparative genomic analyses of S. capitis to provide new insights of commensal scalp isolates from varying skin states, and to expand our current knowledge of the species populations (scalp isolates, n = 59, contextual isolates, n = 127). A highly recombinogenic population structure was revealed, with genomes including the presence of a range of previously described staphylococcal virulence factors, cell wall-associated proteins, and two-component systems. Genomic differences between the two described S. capitis subspecies were explored and reveal determinants associated exclusively with each. The subspecies ureolyticus was distinguished from subspecies capitis by differences in antimicrobial resistance genes and gene clusters linked to survival on the skin. This study will aid further research into classification of S. capitis and virulence linked phylogroups that is important to monitor the spread and evolution of S. capitis.