bluuebunny/crossref_metadata_2025 huggingface dataset:
Caregiver Inclusion in IDEAL Discharge Teaching
Authors: Topham Emily Wahlquist , Bristol Alycia , Luther Brenda , Elmore Catherine E. , Johnson Erin , Wallace Andrea S.
Published: May 2022

Purpose:

Despite recognition that unpaid (e.g., family, friends) caregivers (caregivers) play an important role in successful transitions home after hospitalization, limited information is available about whether and how caregiver experiences of discharge align with current strategies for providing high-quality discharge processes, and how these experiences at discharge impact successful transitions home. The purpose of this study was to explore perceptions of caregivers regarding their discharge preparation, focusing particular attention on whether and how they believed discharge preparation impacted postdischarge patient outcomes.

Methods:

We conducted in-depth, case interviews with four English-speaking caregivers (61–75 years of age). Content analysis was framed by the nature of caregiver involvement proposed by the Agency for Healthcare Research and Quality's (AHRQ's) IDEAL (Include, Discuss, Educate, Assess, Listen) discharge planning strategy.

Results:

Caregivers reported receiving clear discharge instructions, or basic education, and yet felt only passively included in discharge teaching. Once home, the caregivers reported gaps in their knowledge of how to care for the patient, suggesting key gaps related to knowledge of warning signs and problems. Two of the four caregiver participants attributed a hospital readmission to postdischarge knowledge gaps.

Conclusion:

The experiences of these caregivers demonstrate how their limited, passive involvement in discharge education may result in suboptimal patient outcomes after hospitalization. Our findings suggest that structured programs aimed at increasing caregiver involvement in discharge, particularly related to assessment of caregiver problem solving, planning, and postdischarge support, are important in efforts seeking to improve care transitions and postdischarge outcomes.

Implications for Case Management:

This study assesses caregivers' experience with discharge planning and problems they encounter post-discharge, providing case managers with important information regarding the effectiveness of discharge processes. This study of caregiver experiences suggests that the IDEAL discharge planning strategy remains a useful and important framework for case managers to follow when providing discharge services.
The Fate of the Cervical Collar
Authors: Hewes Hilary A. , Ravindra Vijay M. , Ryan Sydney , Russell Katie W. , Soisson Sean , Brockmeyer Douglas L.
Published: May 2022

Objectives

After evaluation and treatment of minor traumatic cervical spine injury (CSI), many children are discharged home in a rigid cervical orthosis (RCO). This study investigated their adherence to RCO treatment recommendations. The feasibility of telehealth cervical spine clearance was also explored.

Methods

This was a prospective observational study of children 3 to 18 years old with mild CSI evaluated at a level I pediatric trauma center from December 1, 2019, through July 31, 2021. Before emergency department discharge, patients received RCO use instructions and recommendation for follow-up with in-person neurosurgery clinic visit, neurosurgery telehealth visit, or in-person primary care provider visit. The family was responsible for arranging follow-up. Primary outcomes included compliance with follow-up and collar use.

Results

Ninety-eight children (mean age, 11.3 ± 4.1 years) were included. Overall, follow-up contact was available for 51 patients (52%). At 1-week follow-up with 36 children, 64% were collar compliant, 13 had no pain (38% remained in RCO), 14 had mild pain without limitations, 8 had pain with some limitations, and 1 had significant pain. At 2-week follow-up with 31 children, 9 (29%) were collar compliant, 23 had no pain, 7 had mild pain without limitations, and 1 with significant persistent pain was found to have an odontoid fracture requiring C1–2 fusion. Patients/families often discontinued the use of the collar without follow-up (47%). Approximately half utilized a recommended clinical follow-up option for clearance, most often in neurosurgery clinic or using a neurosurgery telehealth visit. The mean time to follow-up was 11.34 ± 4.9 days (range, 3–25 days), and mean collar compliance lasted 9.8 ± 5.7 days (range, 1–25 days). No child experienced any short-term complications related to RCO use.

Conclusions

In this pilot study, a substantial portion of children with mild CSIs discharged from the emergency department with an RCO did not adhere to compliance or follow-up recommendations. Persistent pain requires further evaluation.
The Outcome of Cerumen Removal in the Pediatric Emergency Department
Authors: Tavor Oren , Schnapp Zeev , Soffer Gili Palnizky , DeRowe Ari , Rimon Ayelet
Published: May 2022

Objective

Cerumen obstructs the visualization of the tympanic membrane (TM) in up to 40% of children, sometimes posing a challenge to rule out the diagnosis of acute otitis media (AOM) as the source of otalgia (for verbal children), irritability, fever, and febrile seizures. We aim to determine the rate at which removing the cerumen from blocking the view of the TM could change the management of these patients in the pediatric emergency department (PED).

Methods

We retrospectively investigated all medical records of patients who underwent cerumen removal in the PED at a tertiary children's hospital from 2018 to 2019. We analyzed the effect of the procedure on the subsequent workup during their PED visit.

Results

Of 482 children who presented to the PED with otalgia, irritability, fever, and/or febrile seizures and who were referred to an otolaryngologist for subsequent treatment after preliminary evaluation in the PED, 176 were included in the study group after having the cerumen removed from one or both ears. Seventy-three of them were given a diagnosis of AOM, 93 had a normal-appearing TM, and 10 had external otitis. Twenty-one percent of those with AOM and 46% of those with a normal TM (P = 0.008) had blood drawn as part of their workup in their PED visit. The rate of chest x-rays was also significantly less for the AOM group (16% vs 30%, P = 0.03), and they also underwent fewer urine tests (P = NS).

Conclusion

Cerumen removal changes the management of children in the PED who present with a possible diagnosis of an ear infection. Cerumen removal could avoid unnecessary laboratory and imaging studies, which could save time, costs, and suffering.
Steps to Revising the APTA Pediatrics Research Agenda
Authors: Bhat Anjana Narayan ,   APTA Research Agenda Task Force, Fiss Alyssa , O'Neil Margaret , Sansom Jennifer , Heathcock Jill , Dusing Stacey C. , Christy Jennifer
Published: May 2022

The American Physical Therapy Association Academy of Pediatric Physical Therapy (APTA Pediatrics) Research Agenda was updated in spring 2021. This article describes the process used to revise the agenda. A task force of the APTA Pediatrics Research Committee methodically reviewed and revised the 2018-2020 agenda document to reflect the current research priorities important for the field. The research priorities from various federal agencies such as the National Institutes of Health were reviewed and were aligned with the agency research priorities and goals. The agenda was revised based on feedback from task force members, and further revisions were made based on input from select members of APTA Pediatrics and other stakeholders. After incorporating inputs, the agenda was accepted as the APTA Pediatrics Research Agenda for the next 3 years and was shared with the membership on the APTA Pediatrics Research Web site.
Comparing Domain-Specific Self-Efficacy in Pediatric Physical Therapy Education Across Classroom-Based, Online, and Hybrid Curriculum Designs
Authors: Scott Kimberley , Wissinger Jennifer , Maus Elizabeth , Heathcock Jill
Published: May 2022

Purpose:

To describe the pediatric curriculum across 3 years when different instructional designs were used, quantify change in self-efficacy (SE) after completing the curriculum, and define relationships between pediatric experience, SE, and interest in future pediatric practice.

Methods:

Students (N = 137) were included over 3 consecutive years. Instructional design varied across cohorts: classroom-based (n = 48), online (n = 44), and hybrid (n = 45). Pediatric content hours were analyzed. Measures were the Pediatric Communication and Handling Self-Efficacy Scale, pediatric experience, and interest in future pediatric practice.

Results:

Pediatric content hours met published recommendations. Significant growth in SE occurred for all cohorts, with no significant differences in SE scores based on instructional design. Experience and interest in pediatrics were significantly related to communication SE.

Conclusions:

The pediatric physical therapy curriculum delivered via classroom-based, online, or hybrid instruction can be effective in promoting pediatric-specific growth in student SE. Remote pediatric experiential learning is a feasible option for physical therapy programs with limited direct contact with children. What this adds to the evidence: When pediatric curricula meet recommended total hours of instruction, regardless of instructional method or amount of direct laboratory time with real children, pediatric-specific student SE increases. This supports the use of alternative approaches for experiential learning activities in programs with limited access and availability for direct in-person child interactions. Programs may expand integrated clinical experiences (ICE) opportunities to include telehealth when in-person ICE is limited due to distance or availability in nearby clinical settings. Online learning activities (asynchronous or synchronous) may be viable options for laboratory activities when live child volunteers are limited or unavailable. Use of multiple methods of instruction (classroom-based, online, or hybrid) can be beneficial in covering pediatric physical therapy content and improving SE. This evidence can help programs expand their options for exposing student physical therapists to pediatric practice.
Power-building Partnerships for Health: Lessons From Santa Barbara About Building Power to Protect Farmworker Health and Advance Health Equity
Authors: Gaydos Megan , Do-Reynoso Van , Williams Marley , Davalos Hazel , López Arcenio J.
Published: May 2022

The distribution of power in society is “upstream of the upstream” social determinants of health, and community organizers redistribute power to change social and political systems that shape health. Power-building Partnerships for Health (PPH) was launched in 2018 and pairs local public health departments and community organizing groups to support transformational health equity work, prioritizing trust and relationship building as precursors for action. Through PPH, the Santa Barbara County Public Health Department partnered with 2 grassroots organizations, CAUSE and MICOP. This partnership led to their launching a Latinx Indigenous Migrant Health COVID-19 Task Force and to the passing of a first-of-its-kind Health Officer Order on safety in farmworker housing. This practice brief discusses the importance of relationship building and key activities within PPH, and the roles of both the health department and community organizers in taking action to advance health equity in Santa Barbara County during the pandemic.
Allergic Adverse Drug Events After Alert Overrides in Hospitalized Patients
Authors: Luri Marta , Gastaminza Gabriel , Idoate Antonio , Ortega Ana
Published: May 2022

Objectives

This study aimed to assess how often overridden drug allergy alerts (ODAAs) lead to allergic adverse drug events (All-ADEs) and to evaluate the frequency with which drug allergy alerts (DAAs) were overridden and the reasons, as well as appropriateness of these overrides.

Methods

A retrospective observational study of DAA generated between 2014 and 2016 was conducted. The corresponding DAA records were reviewed to determine the frequency of alert overrides. A chart review was performed on a subset of 194 ODAA (the first of every 3 chronologically ordered ODAA) to identify All-ADEs and to evaluate the override reasons and the appropriateness of these overrides.

Results

A total of 2044 DAAs were overridden (override rate of 44.8%). Most were triggered by a nonexact match (93.81%), when ordering nervous system (21.1%) and cardiovascular system (19.6%) drugs and were generated by physicians (72.7%). The main override reason was that the patient was already taking the drug or had previously tolerated the drug. Only 9.28% of ODAAs were inappropriately overridden. Six All-ADEs (3.09%) were identified and were due to anti-infective (1), antineoplastic (1), and iodinated-contrast (4) drug administration. Most All-ADEs were cutaneous and were mild. None was life-threatening or fatal. The All-ADEs rate was higher among inappropriately ODAA (15.79%, P = 0.013).

Conclusions

Alert overrides are not exempt from clinical consequences, although few are associated with All-ADEs. It is necessary to identify the drugs involved in those reactions and to update allergy lists to generate only specific and important DAA and to avoid the negative consequences of overrides.
Toward Constructive Change After Making a Medical Error: Recovery From Situations of Error Theory as a Psychosocial Model for Clinician Recovery
Authors: Harrison Reema , Johnson Judith , McMullan Ryan D. , Pervaz-Iqbal Maha , Chitkara Upma , Mears Steve , Shapiro Jo , Lawton Rebecca
Published: May 2022

Background

Making a medical error is a uniquely challenging psychosocial experience for clinicians. Feelings of personal responsibility, coupled with distress regarding potential or actual patient harm resulting from a mistake, create a dual burden. Over the past 20 years, experiential accounts of making an error have provided evidence of the associated distress and impacts. However, theory-based psychosocial support interventions to improve both individual outcomes for the involved clinicians and system-level outcomes, such as patient safety and workforce retention, are lacking. There is a need for evidence-based ways to both structure and evaluate interventions to decrease the distress of making a medical error and its impacts. Such interventions play a role within wider programs of health professional support. We sought to address this by developing a testable, psychosocial model of clinician recovery after error based on recent evidence.

Methods

Systematic review methodology was used to identify studies published between January 2010 and June 2021 reporting experiences of direct involvement in medical errors and/or subsequent recovery. A narrative synthesis was produced from the resulting articles and used as the basis for a team-based qualitative approach to model building.

Results

We identified 25 studies eligible for inclusion, reporting evidence primarily from experiences of doctors and nurses. The identified evidence indicates that coping approach, conversations (whether they occur and whether they are perceived to be helpful or unhelpful), and learning or development activities (helpful, unhelpful or absent) may influence the relationship between making an error and both individual clinician outcomes of emotional impact and resultant practice change. Our findings led to the development of the Recovery from Situations of Error Theory model, which provides a preliminary theoretical basis for intervention development and testing.

Conclusions

The Recovery from Situations of Error Theory model is the first testable psychosocial model of clinician recovery after making a medical error. Applying this model provides a basis to both structure and evaluate interventions to decrease the distress of making a medical error and its impacts and to support the replication of interventions that work across services and health systems toward constructive change. Such interventions may be embedded into the growing body of peer support and employee support programs internationally that address a diverse range of stressful workplace experiences.
Lessons Learned in Implementing a Chronic Opioid Therapy Management System
Authors: Carlile Narath , Fuller Theresa E. , Benneyan James C. , Bargal Basma , Hunt Lindsay , Singer Sara , Schiff Gordon D.
Published: May 2022

Objectives

Opioid misuse has resulted in significant morbidity and mortality in the United States, and safer opioid use represents an important challenge in the primary care setting. This article describes a research collaborative of health service researchers, systems engineers, and clinicians seeking to improve processes for safer chronic opioid therapy management in an academic primary care center. We present implementation results and lessons learned along with an intervention toolkit that others may consider using within their organization.

Methods

Using iterative improvement lifecycles and systems engineering principles, we developed a risk-based workflow model for patients on chronic opioids. Two key safe opioid use process metrics—percent of patients with recent opioid treatment agreements and urine drug tests—were identified, and processes to improve these measures were designed, tested, and implemented. Focus groups were conducted after the conclusion of implementation, with barriers and lessons learned identified via thematic analysis.

Results

Initial surveys revealed a lack of knowledge regarding resources available to patients and prescribers in the primary care clinic. In addition, 18 clinicians (69%) reported largely “inheriting” (rather than initiating) their chronic opioid therapy patients. We tracked 68 patients over a 4-year period. Although process measures improved, full adherence was not achieved for the entire population. Barriers included team structure, the evolving opioid environment, and surveillance challenges, along with disruptions resulting from the 2019 novel coronavirus.

Conclusions

Safe primary care opioid prescribing requires ongoing monitoring and management in a complex environment. The application of a risk-based approach is possible but requires adaptability and redundancies to be reliable.
Determination of Contrast Timing by Time-Resolved Magnetic Resonance Angiography in Patients With Bidirectional Glenn and Hemi-Fontan Anastomoses
Authors: Yekeler Ensar , Ramirez-Suarez Karen I. , Rapp Jordan B. , White Ammie M. , Otero Hansel J. , Whitehead Kevin K. , Harris Matthew A. , Fogel Mark A. , Biko David M.
Published: May 2022

Purpose

Children with single-ventricle congenital heart disease undergo a series of operations to maintain their pulmonary circulation including bidirectional Glenn (BDG) or hemi-Fontan in the second stage to create a superior cavopulmonary anastomosis. We aimed to optimize cardiovascular angiography protocols by determining optimal contrast timing of pulmonary and systemic circulation on magnetic resonance angiography (MRA) performed with the technique of time-resolved imaging with interleaved stochastic trajectories (TWIST).

Methods and Materials

Cardiac TWIST MRA with lower extremity (LE) contrast injection was analyzed in 92 consecutive patients with a BDG or hemi-Fontan anastomosis. Contrast arrival time to inferior vena cava was set to zero to determine the relative time-to-peak (TTP) of the target vessels. Time-to-peak of each vessel was compared by age (<2 or ≥2 y), ejection fraction (<54% or ≥54%), the median values of heart rate (<111 or ≥111 beats per minute), body surface area (BSA, <0.59 or ≥0.59), cardiac index (<6.04 or ≥6.04), and indexed ascending aorta flow (AscAo_i, <5.3 or ≥5.3). The TTP of the vessels was also correlated with the volumetric parameters.

Results

The mean age of 92 patients (32 female, 60 male) was 3.1 years (0.7–5.6 years). With LE injection, the first peak was depicted in AscAo. Time-to-peak of the pulmonary arteries was approximately 9 seconds later than AscAo. The TTP difference between pulmonary arteries and AscAo was shorter in high heart rate group (8.3 vs 10 seconds, P < 0.001). The TTP difference between AscAo and the mean of pulmonary arteries was significantly shorter in high cardiac index group (8.4 vs 9.9 seconds, P < 0.01) and high AscAo_i group (8.7 vs 9.7 seconds, P = 0.03). The TTP differences were not significant by age, ejection fraction, and BSA. Cardiac index and AscAo_i were negatively correlated with all TTPs except AscAo. The ejection fraction, stroke volume, and atrioventricular regurgitation fraction did not correlate with the TTP.

Conclusions

In patients with BDG or hemi-Fontan anastomosis, TTP of the pulmonary arteries on TWIST MRA via LE intravenous injection is approximately 9 seconds later than AscAo, approximately 8 and 10 seconds later in high and low heart rate groups, respectively. Cardiac index and AscAo_i have less effect on the TTP than the heart rate. There was no TTP difference of the pulmonary arteries by age, BSA, and ejection fraction and no correlation with ejection fraction, stroke volume, and atrioventricular regurgitation fraction. These data can be used to guide timing of pulmonary arterial enhancement of single-ventricle patients after BDG or hemi-Fontan anastomosis.
Ovarian Masses in Patients With Breast Cancer
Authors: Kang Kyung A. , Lee Jonghyun , Kim Hyun-Soo , Park Sung Yoon
Published: May 2022

Purpose

The aim of the study was to investigate the characteristic findings of computed tomography (CT) or magnetic resonance imaging (MRI) to discriminate metastasis from primary ovarian tumors in patients with a history of breast cancer.

Methods

This retrospective study enrolled consecutive 72 patients with a history of breast cancer who underwent surgical confirmation of an ovarian mass detected on CT or MRI (primary ovarian tumors, n = 66; metastases, n = 6). Two independent readers analyzed the grade of solid portions of the ovarian mass using a 5-point scale on CT or MRI. A predominantly cystic mass was defined as a solid grade of 1 to 2. Cancer antigen 125 (CA 125) and the initial stage of breast cancer were also investigated.

Results

The proportions of predominantly cystic masses were significantly different between metastases (0% for both readers) and primary ovarian tumors (59% for reader 1 and 53% for reader 2, P < 0.05). For masses of solid portion grades 3 to 5, CA 125 was significantly higher for malignant epithelial tumors than for the other tumors (P < 0.001), and the initial stage of breast cancer was significantly higher for metastases than for the other tumors (P < 0.001), respectively.

Conclusions

In patients with a history of breast cancer, predominantly cystic masses detected on CT or MRI seem to be primary ovarian tumors. For the other masses, knowledge of CA 125 and initial breast cancer stage may help in the differential diagnosis.
Performance of Automated RAPID Intracranial Hemorrhage Detection in Real-World Practice: A Single-Institution Experience
Authors: Eldaya Rami W. , Kansagra Akash P. , Zei Markus , Mason Evan , Holder Derek , Heitsch Laura , Vo Katie D. , Goyal Manu S.
Published: May 2022

Background and Purpose

Intracranial hemorrhage (ICH) is a common finding in patients presenting to the emergency department with acute neurological symptoms. Noncontrast head computed tomography (NCCT) is the primary modality for assessment and detection of ICH in the acute setting. RAPID ICH software aims to automatically detect ICH on NCCT and was previously shown to have high accuracy when applied to a curated test data set. Here, we measured the test performance characteristics of RAPID ICH software in detecting ICH on NCCT performed in patients undergoing emergency stroke evaluation at a tertiary academic comprehensive stroke center.

Materials and Methods

This retrospective study assessed consecutive patients over a 6-month period who presented with acute neurological symptoms suspicious for stroke and underwent NCCT with RAPID ICH postprocessing. RAPID ICH detection was compared with the interpretation of a reference standard comprising a board-certified or board-eligible neuroradiologist, or in cases of discrepancy, adjudicated by a consensus panel of 3 neuroradiologists. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RAPID ICH for ICH detection were determined.

Results

Three hundred seven NCCT scans were included in the study. RAPID ICH correctly identified 34 of 37 cases with ICH and 228 of 270 without ICH. RAPID ICH had a sensitivity of 91.9% (78.1%–98.3%), specificity of 84.4% (79.6%–88.6%), NPV of 98.7% (96.3%–99.6%), PPV of 44.7% (37.6%–52.1%), and overall accuracy of 85.3% (80.9%–89.1%).

Conclusions

In a real-world scenario, RAPID ICH software demonstrated high NPV but low PPV for the presence of ICH when evaluating possible stroke patients.
Natrinema halophilum sp. nov., Natrinema salinisoli sp. nov., Natrinema amylolyticum sp. nov. and Haloterrigena alkaliphila sp. nov., four extremely halophilic archaea isolated from salt mine, saline soil and salt lake
Authors: Bao Chen-Xi , Li Si-Ya , Xin Yu-Jie , Hou Jing , Cui Heng-Lin
Published: May 2022

Four halophilic archaeal strains, YPL8T, SLN56T, LT61T and KZCA68T, were isolated from a salt mine, saline soil and a salt lake located in different regions of China. Sequence similarities of 16S rRNA and rpoB′ genes among strains YPL8T, SLN56T, LT61T and the current members of

Natrinema

were 94.1–98.2 % and 89.3–95.1 %, respectively, while these values among strain KZCA68T and the current members of

Haloterrigena

were 97.2–97.4 % and 91.7–91.9 %, respectively. The average nucleotide identity, in silico DNA–DNA hybridization and average amino acid identity values among these four strains and their closely related species were all lower than the threshold values for species boundary. All four strains were unable to hydrolyse casein, gelatin, or Tween 80. Strain YPL8T contained phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), disulfated mannosyl glucosyl diether (S2-DGD) and sulfated mannosyl glucosyl diether-phosphatidic acid (S-DGD-PA). Strain SLN56T contained PA, PG, phosphatidylglycerol sulphate (PGS), PGP-Me, S-DGD-1, S2-DGD and S-DGD-PA. Strain LT61T contained PA, PG, PGS, PGP-Me, S-DGD-1 and S2-DGD. The phospholipids of strain KZCA68T were PA, PG and PGP-Me. These results showed that strains YPL8T (=CGMCC 1.13883T=JCM 31181T), SLN56T (=CGMCC 1.14945T=JCM 30832T) and LT61T (=CGMCC 1.14942T=JCM 30668T) represent novel species of the genus

Natrinema

, for which the names, Natrinema halophilum sp. nov., Natrinema salinisoli sp. nov. and Natrinema amylolyticum sp. nov. are proposed. Strain KZCA68T (=CGMCC 1.17211T=JCM 34158T) represents a novel species of

Haloterrigena

, for which the name Haloterrigena alkaliphila sp. nov. is proposed.
A Monte Carlo Estimation of the Narrow-Sense Heritability of COVID-19 Infection and Severity from AncestryDNA Survey Data
Authors: Averitt Amelia J. , Sharma Deepika , Cantor Michael
Published: May 2022

Respiratory infectious diseases, such as COVID-19, demonstrate a host genetic component that contributes to interindividual differences of susceptibility and infection. At present, the relative effect of environmental and genetic factors of COVID-19 is unknown. This research presents a Monte Carlo (MC) estimation of the genetic narrow-sense heritability of COVID-19 infection and severity from AncestryDNA survey data. The results suggest a moderate genetic contribution to COVID-19 infection and a low genetic contribution for COVID-19 severity.
STAKEHOLDER PERCEPTION ABOUT ADOLESCENT REPRODUCTIVE HEALTH EDUCATION IN THE UPPER EAST REGION OF GHANA
Authors: Gariba Evans Bagura , Hadjez Esteban
Published: May 2022

Reproductive Health Education has been seen as a form of Comprehensive Sexual Education which combines health and right-based strategies to empower communities to enhance their well-being. From a health promotion perspective, this study explores stakeholder perception about Reproductive Health Education in the Upper East Region of Ghana where adolescent needs and outcome are challenged. These finding gives an in-depth understanding of reproductive health education from stakeholders’ perspective as being a double-edge sword.
O-GlcNAc transferase contributes to sex-specific placental deregulation in gestational diabetes
Authors: Cui Yiwen , Cruz Meredith , Palatnik Anna , Olivier-Van Stichelen Stephanie
Published: May 2022

Fetal sex has been known to be associated with differential risks for adverse perinatal outcomes. Recently it has been highlighted as a risk factor for gestational diabetes (GDM), which carries short- and long-term cardiometabolic implications for the pregnant women and their offspring. Understanding the molecular mechanisms through which fetal sex can modulate placenta physiology can help identify novel molecular targets for future clinical applications. In this study, we investigated the nutrient-sensing O-GlcNAc pathway as a potential mediator of sex-driven placenta dysfunction due to the unique location of the O-GlcNAc transferase (OGT) enzyme on the X chromosome. Using banked placenta tissues, we demonstrated that placenta OGT is downregulated in women with GDM, especially when carrying a male offspring. We modeled our observation in vitro using male placenta trophoblast BeWo cells in which OGT was knocked down. A comprehensive transcriptomic profile via RNA sequencing demonstrated changes in hormonal, inflammatory and immunologic markers, toward GDM-like transcriptional signatures. Altogether, this study suggests that OGT deserves important consideration for sexual dimorphism observed in GDM and highlights the importance of O-GlcNAcylation in placenta endocrine physiology.
Candidate effector proteins from the maize tar spot pathogenPhyllachora maydislocalize to diverse plant cell compartments
Authors: Helm Matthew , Singh Raksha , Hiles Rachel , Jaiswal Namrata , Myers Ariana , Iyer-Pascuzzi Anjali S. , Goodwin Stephen B.
Published: May 2022

Most fungal pathogens secrete effector proteins into host cells to modulate their immune responses, thereby promoting pathogenesis and fungal growth. One such fungal pathogen is the ascomycetePhyllachora maydis, which causes tar spot disease on leaves of maize (Zea mays). Sequencing of theP. maydisgenome revealed 462 putatively secreted proteins of which 40 contain expected effector-like sequence characteristics. However, the subcellular compartments targeted byP. maydiseffector candidate (PmECs) proteins remain unknown and it will be important to prioritize them for further functional characterization. To test the hypothesis that PmECs target diverse subcellular compartments, cellular locations of super Yellow Fluorescent Protein (sYFP)-taggedP. maydiseffector candidate proteins were identified using aNicotiana benthamiana-based heterologous expression system. Immunoblot analyses showed that most of the PmEC-fluorescent protein fusions accumulated protein inN. benthamiana, indicating the candidate effectors could be expressed in dicot leaf cells. Laser-scanning confocal microscopy ofN. benthamianaepidermal cells revealed most of theP. maydisputative effectors localized to the nucleus and cytosol. One candidate effector, PmEC01597, localized to multiple subcellular compartments including the nucleus, nucleolus, and plasma membrane while an additional putative effector, PmEC03792, preferentially labelled both the nucleus and nucleolus. Intriguingly, one candidate effector, PmEC04573, consistently localized to the stroma of chloroplasts as well as stroma-containing tubules (stromules). Collectively, these data suggest effector candidate proteins fromP. maydistarget diverse cellular organelles and may thus provide valuable insights into their putative functions as well as host processes potentially manipulated by this fungal pathogen.
Deletion mapping of regulatory elements for GATA3 reveals a distal T helper 2 cell enhancer involved in allergic diseases
Authors: Chen Hsiuyi V. , Fiaux Patrick C. , Sen Arko , Luthra Ishika , Ho Aaron J. , Chen Aaron R. , Guruvayurappan Karthik , Lorenzini Michael H. , O’Connor Carolyn , McVicker Graham
Published: May 2022

The GATA3 gene is essential for T cell differentiation and is surrounded by risk variants for immune traits. Interpretation of these variants is challenging because the regulatory landscape of GATA3 is complex with dozens of potential enhancers spread across a large topological associating domain (TAD) and gene expression quantitative trait locus (eQTL) studies provide limited evidence for variant function. Here, we perform a tiling deletion screen in Jurkat T cells to identify 23 candidate regulatory elements. Using small deletions in primary T helper 2 (Th2) cells, we validate the function of five of these elements, two of which contain risk variants for asthma and allergic diseases. We fine-map genome-wide association study (GWAS) signals in a distal regulatory element, 1 Mb downstream, to identify 14 candidate causal variants. Small deletions spanning candidate rs725861 decrease GATA3 expression in Th2 cells suggesting a causal mechanism for this variant in allergic diseases. Our study demonstrates the power of integrating GWAS signals with deletion mapping and identifies critical regulatory sequences for GATA3.
Coral environmental history is primary driver of algal symbiont composition, despite a mass bleaching event
Authors: de Souza Mariana Rocha , Caruso Carlo , Ruiz-Jones Lupita , Drury Crawford , Gates Ruth D. , Toonen Robert J.
Published: May 2022

Coral reefs are iconic examples of climate change impacts because climate-induced heat stress causes the breakdown of the coral-algal symbiosis leading to a spectacular loss of color, termed ‘coral bleaching’. To examine the fine-scale dynamics of this process, we re-sampled 600 individually marked Montipora capitata colonies from across Kāne‘ohe Bay, Hawai’i and compared the algal symbiont composition before and after the 2019 bleaching event. The relative proportion of the heat-tolerant symbiont Durusdinium in corals increased in most parts of the bay following the bleaching event. Despite this widespread increase in abundance of Durusdinium, the overall algal symbiont community composition was largely unchanged, and hydrodynamically defined regions of the bay retained their distinct pre-bleaching compositions. Furthermore, depth and temperature variability were the most significant drivers of Symbiodiniaceae community composition by site regardless of bleaching intensity or change in relative proportion of Durusdinium. Our results suggest that the plasticity of symbiont composition in corals may be constrained to adaptively match the long-term environmental conditions surrounding the holobiont, independent of an individual coral’s stress and bleaching response.
Celloscope: a probabilistic model for marker-gene-driven cell type deconvolution in spatial transcriptomics data
Authors: Geras Agnieszka , Shafighi Shadi Darvish , Domżał Kacper , Filipiuk Igor , Rączkowski Łukasz , Toosi Hosein , Kaczmarek Leszek , Koperski Łukasz , Lagergren Jens , Nowis Dominika , Szczurek Ewa
Published: May 2022

Spatial transcriptomics maps gene expression across tissues, posing the challenge of determining the spatial arrangement of different cell types. However, spatial transcriptomics spots contain multiple cells. Therefore, the observed signal comes from mixtures of cells of different types. Here, we propose an innovative probabilistic model, Celloscope, that utilizes established prior knowledge on marker genes for cell type deconvolution from spatial transcriptomics data. Celloscope outperformed other methods on simulated data, successfully indicated known brain structures and spatially distinguished between inhibitory and excitatory neuron types based in mouse brain tissue, and dissected large heterogeneity of immune infiltrate composition in prostate gland tissue.
Improving and evaluating deep learning models of cellular organization
Authors: Sun Huangqingbo , Fu Xuecong , Abraham Serena , Shen Jin , Murphy Robert F
Published: May 2022

Motivation

Cells contain dozens of major organelles and thousands of other structures, many of which vary extensively in their number, size, shape and spatial distribution. This complexity and variation dramatically complicates the use of both traditional and deep learning methods to build accurate models of cell organization. Most cellular organelles are distinct objects with defined boundaries that do not overlap, while the pixel resolution of most imaging methods is not sufficient to resolve these boundaries. Thus while cell organization is conceptually object-based, most current methods are pixel-based. Using extensive image collections in which particular organelles were fluorescently-labeled, deep learning methods can be used to build conditional autoencoder models for particular organelles. A major advance occurred with the use of a U-net approach to make multiple models all conditional upon a common reference, unlabeled image, allowing the relationships between different organelles to be at least partially inferred.

Results

We have developed improved GAN-based approaches for learning these models and have also developed novel criteria for evaluating how well synthetic cell images reflect the properties of real images. The first set of criteria measure how well models preserve the expected property that organelles do not overlap. We also developed a modified loss function that allows retraining of the models to minimize that overlap. The second set of criteria uses object-based modeling to compare object shape and spatial distribution between synthetic and real images. Our work provides the first demonstration that, at least for some organelles, deep learning models can capture object-level properties of cell images.

Availability

A Reproducible Research Archive containing all source code, generated images and analysis results will be made available at http://murphylab.cbd.cmu.edu/Software upon publication.

Contact

murphy@cmu.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Transcriptional control of adipogenesis by PATZ1
Authors: Patel Sanil , Sparman Njeri , Sadeh Shani , Wang Jeixin , Whitelegge Julian P. , Fried Susan K. , Waki Hironori , Villanueva Claudio J. , Seldin Marcus , Sakaguchi Shinya , Ellmeier Wilfried , Tontonoz Peter , Rajbhandari Prashant
Published: May 2022

White adipose tissues (WAT) play a central role in lipid storage and systemic energy, lipid, and glucose homeostasis. Understanding the intricacies of adipocyte formation could inform therapies for obesity and metabolic disorders. We have identified the POZ/BTB and AT Hook Containing Zinc Finger 1 (PATZ1) protein as an adipogenic transcription factor through an unbiased high-throughput cDNA screen for modulators of adipogenesis. PATZ1 is expressed by both human and mouse adipocyte precursor cells (APC) and adipocytes, and its expression negatively correlates with obesity. In cell models, PATZ1 expression promotes adipogenesis through a mechanism dependent on protein-protein interaction and DNA binding. Adipose-specific ablation of PATZ1 in mice leads to decreased lipid storage and fat mass and protection from diet-induced obesity. Genome-wide PATZ1 DNA binding analyses using ChIP-Seq suggest that PATZ1 facilitates adipogenesis through interactions with transcription factor machinery at the promoter regions of key adipogenic factors and histone modifiers. Global PATZ1 protein interaction studies using immunoprecipitation-mass spectrometry (IP-MS) suggest that General Transcription Factor 2I (GTF2I) binding to PATZ1 forms a repressive complex, and knockdown of GTF2I augments PATZ1 adipogenic function. Collectively these findings identify PATZ1 as a regulator of the adipocyte differentiation programs and advance our understanding of the complex transcriptional mechanisms underlying adipose tissue development and homeostasis.
Synechococcusnitrogen gene loss in iron-limited ocean regions
Authors: Sharpe Garrett , Zhao Liang , Meyer Meredith G. , Gong Weida , Burns Shannon M. , Tagliabue Allesandro , Buck Kristen N. , Santoro Alyson E. , Graff Jason R. , Marchetti Adrian , Gifford Scott
Published: May 2022

Synechococcusare the most abundant cyanobacteria in high latitude regions and are responsible for an estimated 17% of annual marine primary productivity. Despite their biogeochemical importance,Synechococcuspopulations have been unevenly sampled across the ocean, with most studies focused on low-latitude strains. In particular, the near absence ofSynechococcusgenomes from high-latitude, High Nutrient Low Chlorophyll (HNLC) regions leaves a gap in our knowledge of picocyanobacterial adaptation to iron limitation and their influence on carbon, nitrogen, and iron cycles. We examinedSynechococcuspopulations from the subarctic North Pacific, a well-characterized HNLC region, with quantitative metagenomics. Assembly with short and long reads produced two near completeSynechococcusmetagenome-assembled genomes (MAGs). Quantitative metagenome-derived abundances of these populations matched well with flow cytometry counts, and theSynechococcusMAGs were estimated to comprise >99% of theSynechococcusat Station P. Whereas the Station PSynechococcusMAGs contained multiple genes for adaptation to iron limitation, both genomes lacked genes for uptake and assimilation of nitrate and nitrite, suggesting a dependence on ammonium, urea, and other forms of recycled nitrogen leading to reduced iron requirements. A global analysis ofSynechococcusnitrate reductase abundance in the TARA Oceans dataset found nitrate assimilation genes are also lower in other HNLC regions. We propose nitrate and nitrite assimilation gene loss inSynechococcusrepresents an adaptation to severe iron limitation in high-latitude regions where ammonium availability is higher. Our findings have implications for models that quantify the contribution of cyanobacteria to primary production and subsequent carbon export.

Significance

The cyanobacteriumSynechococcusis a major contributor to ocean primary production and biogeochemistry. Here, we used quantitative metagenomics to assemble and enumerate twoSynechococcusgenomes from an iron-limited, High Nutrient Low Chlorophyll region. We show these genomes represent the majority ofSynechococcuscells at the site and are the first knownSynechococcusunable to assimilate either nitrate or nitrite. This gene loss is likely due to the high iron quota of these proteins and predominant availability of recycled forms of nitrogen.Synechococcus’loss of nitrate assimilation affects their role in elemental cycles (e.g., carbon, nitrogen, and iron), limits their potential for carbon export, and enhances our understanding ofSynechococcusevolution in response to nutrient limitation and competition.
How important is budding speciation for comparative studies?
Authors: Caetano Daniel S. , Quental Tiago Bosisio
Published: May 2022

The acknowledgment of evolutionary dependence among species has fundamentally changed how we ask biological questions. Phylogenetic models became the standard approach for studies with three or more lineages, in particular those using extant species. Most phylogenetic comparative methods (PCMs) translate relatedness into covariance, meaning that evolutionary changes before lineages split should be interpreted together whereas after the split lineages are expected to change independently. This clever realization has shaped decades of research. Here we discuss one element of the comparative method often ignored or assumed as unimportant: if nodes of a phylogeny represent the dissolution of the ancestral lineage into two new ones or if the ancestral lineage can survive speciation events (i.e., budding). Budding speciation is often reported in paleontological studies, due to the nature of the evidence for budding in the fossil record, but it is surprisingly absent in comparative methods. Here we show that many PCMs assume that divergence happens as a symmetric split, even if these methods don’t explicitly mention this assumption. We discuss the properties of trait evolution models for continuous and discrete traits and their adequacy under a scenario of budding speciation. We discuss the effects of budding speciation under a series of plausible evolutionary scenarios and show when and how these can influence our estimates. We also propose that long-lived lineages that have survived through a series of budding speciation events and given birth to multiple new lineages can produce evolutionary patterns that challenge our intuition about the most parsimonious history of trait changes in a clade. We hope our discussion can help bridge comparative approaches in paleontology and neontology as well as foster awareness about the assumptions we make when we use phylogenetic trees.
The TCR Cα domain regulates responses to self-pMHCII
Authors: Kim Caleb Y. , Parrish Heather L. , Kuhns Michael S.
Published: May 2022

T-cells play a central role in adaptive immunity by recognizing peptide-antigens presented in MHC molecules (pMHC) via their clonotypic T-cell receptors (TCRs). αβTCRs are heterodimers, consisting of TCRα and TCRβ subunits that are composed of variable (Vα, Vβ) and constant (Cα, Cβ) domains. While the Vα, Vβ, and Cβ domains adopt typical immunoglobulin (Ig) folds in the extracellular space, the Cα domain lacks a top β sheet and instead has two loosely associated top strands (C and F strands) on its surface. Previous results suggest that this unique Ig-like fold mediates homotypic TCR interactions and influences signalingin vitro. To better understand why evolution has selected this unique structure, we asked: what is the fitness cost for development and function of CD4+T cells bearing a mutation in the Cα C-strand? In both TCR retrogenic and transgenic mice we observed increased single positive thymocytes bearing mutant TCRs compared with those expressing wild type TCRs. Furthermore, our analysis of mutant TCR transgenic mice revealed an increase in naive CD4+T cells experiencing strong tonic TCR signals, increased homeostatic survival, and increased recruitment of responders to cognate pMHCII upon immunization, compared to wild type. The mutation did not, however, overtly impact CD4+T cell proliferation or differentiation after immunization. We interpret these data as evidence that the unique Cα domain has evolved to fine-tune TCR signaling, particularly in response to weak interactions with self-pMHCII.
Short tandem repeats bind transcription factors to tune eukaryotic gene expression
Authors: Horton Connor A. , Alexandari Amr M. , Hayes Michael G. B. , Marklund Emil , Schaepe Julia M. , Aditham Arjun K. , Shah Nilay , Shrikumar Avanti , Afek Ariel , Greenleaf William J. , Gordân Raluca , Zeitlinger Julia , Kundaje Anshul , Fordyce Polly M.
Published: May 2022

Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and their polymorphisms alter gene expression, yet how they regulate transcription remains unknown. We find that STRs can modulate transcription factor (TF)-DNA affinities and on rates by up to 70-fold by directly binding TF DNA-binding domains, with energetic impacts approaching or exceeding mutations to consensus sites. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density near motifs to speed target search. Confirming that STRs also impact TF binding in cells, neural networks trained only on in vivo occupancies predict identical effects to those observed in vitro. Approximately 90% of TFs preferentially bind STRs that need not resemble known motifs, providing a novel cis-regulatory mechanism to target TFs to cognate sites.