bluuebunny/crossref_metadata_2025 huggingface dataset:
Cash transfers and nutrition education to improve dietary diversity among children aged 6–23 months in Grand Gedeh County, Liberia: a cluster-randomized trial
Authors: Rees Chris A , Cleon Dadah , Davis Annette B , Sammy Andrew M , Britto Carl D , Massaquoi Wesley , Forkpa Oretha W , Johnson Andrew J , Hook Varla F , MaCauley Jane A , Pewu Garbie F , Gorpue Mercy , Gborie Amos , Brown Trokon T , Fannieh Augustine , Dweh Teeline , Marley Ruth B , Baysah Massaboi K , Nowine Netus N , Niescierenko Michelle , Zaizay Leela
Published: November 2022

Objectives

To evaluate the efficacy of a cash transfer and nutrition education program on dietary diversity among children in Liberia. We hypothesized that a multi-pronged intervention would result in improved dietary diversity among children.

Methods

We conducted a three-armed, cluster-randomized study in 42 communities (12 children per community) in Grand Gedeh County, Liberia, over a 12-month period. We randomly assigned communities to control (n = 14 communities), those that received both bimonthly cash transfers and a structured nutrition education program (n = 14 communities) and those that received bimonthly cash transfers alone (n = 14 communities). Community health assistants conducted bimonthly assessments in participants’ homes. The primary outcome was the proportion of children aged 6–23 months who met minimum dietary diversity score (i.e., ≥4 food groups consumed per day). Secondary outcomes included meal frequency and healthcare utilization for illnesses (NCT04101487).

Results

There were 599 children enrolled; 533 (88.9%) were retained through the trial period. The proportion of children who consumed ≥4 food groups per day did not differ among the three arms. However, children randomized to receive cash transfers had higher dietary diversity scores than the control group. Children in communities that received cash transfers alone and with nutrition education consumed significantly more meals per day and were less likely to have visits to clinics or hospitals for illnesses than children in control communities.

Conclusion

Bimonthly, unconditional cash transfers and nutrition education were associated with higher dietary diversity scores, greater meal frequency, and fewer healthcare visits for illnesses among children aged 6–23 months.
Severe acute malnutrition outcomes for children of South African compared to foreign-born parents admitted to a rural regional hospital in South Africa: a retrospective cohort study
Authors: Thomas Aldona , Engelbrecht Arnoldus L , Slogrove Amy L
Published: November 2022

Background

Children of foreign-born parents with vulnerable legal status, limited economic rights and exclusion from national social interventions may be at higher risk for severe acute malnutrition (SAM). We evaluated the relationship between parent status (foreign-born vs. South African) and outcomes for children with SAM admitted to a rural regional hospital in the Western Cape, South Africa.

Methods

A retrospective cohort study was conducted including children <5 years admitted to Worcester Provincial Hospital during 2015–17 with SAM (WHO weight-for-height Z score <−3, presence of nutritional oedema, mid-upper-arm-circumference of <11.5 cm or visible severe wasting). Exposures, including parent status, and outcomes including in-hospital death were determined from hospital and regional dietician records.

Results

Of 95 children included, 31 (33%) were of foreign-born and 64 (67%) of South African parents. Median (interquartile range) age at admission was 12 (8–18) vs. 10 (8–13) months in children of South African vs. foreign-born parents with no difference in preterm birth, concurrent illnesses or admission duration. Age, HIV status and breastfeeding practices were no different in foreign-born compared to South African mothers. In-hospital deaths occurred in 3/64 (5%) and 6/31 (19%) children of South African vs. foreign-born parents (p = 0.01). Children of foreign-born compared to South African parents had an odds ratio of 4.88 (95% CI 1.13–21.06) for in-hospital SAM-associated mortality.

Conclusion

In this rural setting, 33% of children admitted with SAM were of foreign-born parents and experienced in-hospital SAM-associated mortality at least four times higher than children of South African parents. This illustrates the extreme vulnerability of these children.
XIVModern Literature
Authors: Ross Shawna , Mourant Chris , Fischer Tiana M , Phillips Joshua , Parsons Katherine , Stringfellow Sophie , RodrÍguez MartÍn Gustavo A , Saunders Graham , Richards Joshua , Quin Jack
Published: November 2022

This chapter has eight sections 1. General. 2. Fiction Pre-1945; 3. Fiction Post-1945; 4. Drama Pre-1950; 5. Drama Post-1950; 6. British Poetry Pre-1950; 7. British Poetry Post-1950; 8. Modern Irish Poetry. Section 1 is by Shawna Ross; section 2(a) is by Chris Mourant; section 2(b) will resume in 2023; section 2(c) is by Tiana M. Fischer; section 2(d) will resume in 2023; section 2(e) is by Joshua Phillips; section 3(a) is by Katherine Parsons; section 3(b) will resume in 2023; section 4(a) is by Sophie Stringfellow; section 4(b) is by Gustavo A. Rodríguez Martín; section 5 is by Graham Saunders; section 6(a) will resume in 2023, section 6(b) is by Joshua Richards; section 7 will resume in 2023; section 8 is by Jack Quin.
Using Resident-Sensitive Quality Measures Derived From Electronic Health Record Data to Assess Residents’ Performance in Pediatric Emergency Medicine
Authors: Smirnova Alina , Chahine Saad , Milani Christina , Schuh Abigail , Sebok-Syer Stefanie S. , Swartz Jordan L. , Wilhite Jeffrey A. , Kalet Adina , Durning Steven J. , Lombarts Kiki M.J.M.H. , van der Vleuten Cees P.M. , Schumacher Daniel J.
Published: November 2022

Purpose

Traditional quality metrics do not adequately represent the clinical work done by residents and, thus, cannot be used to link residency training to health care quality. This study aimed to determine whether electronic health record (EHR) data can be used to meaningfully assess residents’ clinical performance in pediatric emergency medicine using resident-sensitive quality measures (RSQMs).

Method

EHR data for asthma and bronchiolitis RSQMs from Cincinnati Children’s Hospital Medical Center, a quaternary children’s hospital, between July 1, 2017, and June 30, 2019, were analyzed by ranking residents based on composite scores calculated using raw, unadjusted, and case-mix adjusted latent score models, with lower percentiles indicating a lower quality of care and performance. Reliability and associations between the scores produced by the 3 scoring models were compared. Resident and patient characteristics associated with performance in the highest and lowest tertiles and changes in residents’ rank after case-mix adjustments were also identified.

Results

274 residents and 1,891 individual encounters of bronchiolitis patients aged 0–1 as well as 270 residents and 1,752 individual encounters of asthmatic patients aged 2–21 were included in the analysis. The minimum reliability requirement to create a composite score was met for asthma data (α = 0.77), but not bronchiolitis (α = 0.17). The asthma composite scores showed high correlations (r = 0.90–0.99) between raw, latent, and adjusted composite scores. After case-mix adjustments, residents’ absolute percentile rank shifted on average 10 percentiles. Residents who dropped by 10 or more percentiles were likely to be more junior, saw fewer patients, cared for less acute and younger patients, or had patients with a longer emergency department stay.

Conclusions

For some clinical areas, it is possible to use EHR data, adjusted for patient complexity, to meaningfully assess residents’ clinical performance and identify opportunities for quality improvement.
An Initial miRNA Profile of Persons With Persisting Neurobehavioral Impairments and States of Disordered Consciousness After Severe Traumatic Brain Injury
Authors: Zilliox Michael J. , Foecking Eileen M. , Kuffel Gina R. , Conneely Mark , Saban Karen L. , Herrold Amy A. , Kletzel Sandra L. , Radke Jay R. , Walsh Elyse , Guernon Ann , Pape Ariana , Ripley David L. , Patil Vijaya , Pacheco Marilyn S. , Rosenow Joshua M. , Bhaumik Runa , Bhaumik Dulal , Pape Theresa L. Bender
Published: November 2022

Objective:

To examine the merits of using microRNAs (miRNAs) as biomarkers of disorders of consciousness (DoC) due to traumatic brain injury (TBI).

Settings:

Acute and subacute beds.

Participants:

Patients remaining in vegetative and minimally conscious states (VS, MCS), an average of 1.5 years after TBI, and enrolled in a randomized clinical trial (n = 6). Persons without a diagnosed central nervous system disorder, neurotypical controls (n = 5).

Design:

Comparison of whole blood miRNA profiles between patients and age/gender-matched controls. For patients, correlational analyses between miRNA profiles and measures of neurobehavioral function.

Main Measures:

Baseline measures of whole blood miRNAs isolated from the cellular and fluid components of blood and measured using miRNA-seq and real-time polymerase chain reaction (RT-PCR). Baseline neurobehavioral measures derived from 7 tests.

Results:

For patients, relative to controls, 48 miRNA were significantly (P < .05)/differentially expressed. Cluster analysis showed that neurotypical controls were most similar to each other and with 2 patients (VS: n = 1; and MCS: n = 1). Three patients, all in MCS, clustered separately. The only female in the sample, also in MCS, formed an independent group. For the 48 miRNAs, the enriched pathways identified are implicated in secondary brain damage and 26 miRNAs were significantly (P < .05) correlated with measures of neurobehavioral function.

Conclusions:

Patients remaining in states of DoC an average of 1.5 years after TBI showed a different and reproducible pattern of miRNA expression relative to age/gender-matched neurotypical controls. The phenotypes, defined by miRNA profiles relative to persisting neurobehavioral impairments, provide the basis for future research to determine the miRNA profiles differentiating states of DoC and the basis for future research using miRNA to detect treatment effects, predict treatment responsiveness, and developing targeted interventions. If future research confirms and advances reported findings, then miRNA profiles will provide the foundation for patient-centric DoC neurorehabilitation.
Clozapine Blood Concentration Predicts Corrected QT-Interval Prolongation in Patients With Psychoses
Authors: Kim Kyungtae , Kim Yong Sik , Joo Eun-jeong , Kim Eui-joong , Bhang Soo-young , Choi Jae-won , Jeong Jae Hoon , Lee Kyu Young
Published: November 2022

Background

Corrected QT-interval (QTc) prolongation (QTP) is a rare but fatal adverse effect of antipsychotics. Clozapine is the only antipsychotic recommended for treatment of resistant schizophrenia; however, clozapine has been reported to cause QTP. We sought factors predictive of QTP in patients who had antipsychotic polypharmacy involving clozapine. We explored whether the clozapine blood concentration might predict QTP.

Methods

We included 133 patients with schizophrenia spectrum disorder who had antipsychotic polypharmacy involving clozapine. We used the χ
2 and nonparametric tests to compare clozapine therapeutic drug monitoring (TDM) values and QTc-prolonged person (QTPP) status. Multivariate regression and mediator models were used to identify risk factors for QTPP status and QTP.

Results

In total, 111 patients were prescribed clozapine. The QTPP rates were 31.3% (20) for men and 23.2% (16) for women. Compared with the non-QTPP group, the QTPP group exhibited significantly higher daily dose of all antipsychotics including clozapine, a higher clozapine dose, and elevated clozapine and norclozapine TDM values. Furthermore, such patients were prescribed a greater number of antipsychotics. Multivariate logistic regression revealed that only the clozapine TDM value could be predictive factor for QTPP status (P = 0.018). A clozapine TDM value above the therapeutic range (>600 mg/dL) was associated with a high risk of QTPP status (adjusted odds ratio, 6.5; 95% confidence interval, 1.7–25.2; P = 0.006). The mediator model revealed that the clozapine TDM values completely mediated the association between the clozapine dose and the QTc interval.

Conclusions

The clozapine blood concentration reliably predicts QTP in patients with clozapine use.
How Do Hospital-Specific Data Dictionaries Impact Competency Level With Data Collection: A National Survey
Authors: Urban Shane , Carmichael Heather , Vasilatos Angela , Moe Martin , Dumond Robbie , Kennard Lori , Vega Stephanie , Krell Regina , Cripps Michael W. , Velopulos Catherine
Published: November 2022

Background:

Trauma registry staff are tasked with high-quality data collection to support program requirements. Hospital-specific data dictionaries are increasingly used to ensure accurate data collection, yet it is unknown how such a resource impacts a trauma registry team's competency with data collection.

Objective:

This study sought to explore whether having a hospital-specific data dictionary affected trauma service team members' self-reported competency level with abstracting required and nonrequired data elements.

Methods:

This study used an anonymous, cross-sectional survey distributed (July 2020 to September 2020) by the Society of Trauma Nurses, the American College of Surgeons, and the Trauma System News outlets to trauma registrars, trauma nurse coordinators, clinical quality specialists, program managers, program directors, and trauma research personnel. A 26-question survey was designed using a visual sliding scale from 0 to 100 to measure self-reported competence and associated variables.

Results:

A total of 881 respondents completed the survey from at least 495 centers. Six hundred ninety-six (79.0%) respondents were from Level I or Level II programs. Several factors were associated with team members feeling highly competent in collecting data for various reporting requirements, including the level of trauma center verification, tenure working in trauma services, and the presence of a hospital-specific data dictionary.

Conclusion:

Trauma centers should consider establishing a hospital-specific data dictionary as they are associated with higher registry staff competence working with trauma registry data.
Reliability and Validity of the Japanese Version of the Attitudes Related to Trauma-Informed Care (ARTIC-10) Scale
Authors: Kataoka Mayumi , Kotake Risa , Asaoka Hiroki , Miyamoto Yuki , Nishi Daisuke
Published: November 2022

Background:

Trauma-informed care is recommended to avoid the inadvertent retraumatization of patients by health care providers. Psychometric evaluation of trauma-informed care instruments is needed. The Japanese version of the Attitudes Related to Trauma-Informed Care (ARTIC-10) Scale has not yet been psychometrically validated.

Objective:

The study's objective was to examine the reliability and validity of the ARTIC-10.

Methods:

This psychometric study of the ARTIC-10 compared with five other scales associated with attitudes related to trauma-informed care used a cross-sectional survey design conducted in November 2020 with a convenience sample of Japanese physicians and nurses recruited from an internet research agency. Participants completed self-administered questionnaires including the (a) ARTIC-10; (b) the Japanese version of the Moral Sensitivity Questionnaire 2018; (c) Patient Health Questionnaire-9; (d) Generalized Anxiety Disorder-7; (e) Stress Underestimation Beliefs; and (f) Negative Acts Questionnaire-Revised. Cronbach's α measured reliability internal consistency, and construct validity was measured by Spearman's rank.

Results:

A total of 794 physicians and nurses completed the surveys. Cronbach's α value of ARTIC-10 was 0.56. Higher scores of ARTIC-10 were positively and significantly correlated with Moral Sensitivity Questionnaire 2018 and negatively and significantly correlated with other scales (r =−.12 to .30).

Conclusion:

This study found only modest internal consistency and construct validity of the Japanese version of ARTIC-10 in physicians and nurses. Further study is needed to identify factors that affect the reliability and validity of this Japanese scale to improve its psychometric properties.
Preventing Vitamin B6–Related Neurotoxicity
Authors: Reddy Pramod
Published: November 2022

Background:

Vitamin B6 is essential for life and plays a critical role in many biochemical and physiological processes in the human body. The term B6 collectively refers to 6 water-soluble vitamers, and only the pyridoxal 5′-phosphate (PLP) serves as the biologically active form. A plasma PLP concentration above 30 nmol/L (7.4 μg/L) is indicative of an adequate vitamin B6 status for all age and sex groups. The currently recommended daily allowance of B6 (1.5–2 mg/d) from dietary sources frequently results in inadequate B6 status (<20 nmol/L or 5 μg/L) in many elderly patients and patients with comorbid conditions. PLP-based supplements are preferred and should be administered weekly in low doses (50–100 mg) to maintain a stable serum PLP level between 30 and 60 nmol/L or 7.4 and 15 μg/L.

Areas of Uncertainty:

It is challenging for physicians to prescribe a safe dose of B6 supplements because of the narrow therapeutic index. The association between elevated levels of pyridoxine and neuropathy is not well established. PLP-based supplements are shown to be least neurotoxic, but further clinical trials are needed to establish the long-term safety in high doses.

Data Sources:

PubMed search of randomized control trials and meta-analyses.

Therapeutic Opinion:

Plasma B6 levels should be ordered as a part of workup of any unexplained anemia before labeling as “anemia of chronic disease.” B6 supplementation is also crucial in the management of chronic Mg deficiency resistant to therapy. When B6 is administered daily in supraphysiologic doses, there is a potential for the development of neurotoxicity (typically at levels >100 nmol/L or 25 μg/L). PLP-based supplements are preferred over pyridoxine supplements because of minimal neurotoxicity observed in neuronal cell viability tests. Since B6 metabolites have a long half-life, weekly administration is preferred over daily use to prevent toxicity.
Caregiver Burden Correlates With Complexity of Drug Regimen in Non-oncological Palliative Medicine
Authors: Pop Rodica Sorina , Mosoiu Daniela , Tint Diana
Published: November 2022

Background:

Progressive chronic diseases presume a complex treatment plan that depends on the number of symptoms, their severity, and comorbidities. Drug management is an essential responsibility of the family caregiver of a palliative care patient, but has received limited attention in field research.

Study Questions:

The aim of this study is to identify the complexity of the therapeutic plan followed at home by cancer or noncancer patients needing palliative care, and to assess its impact on the burden of the family caregivers.

Study Design:

This observational study was conducted at patient's admission in a palliative care department. The study involved cancer and noncancer patients and their primary family caregivers. To measure the care burden, the Burden Scale for Family Caregiver was used and for the complexity of the therapeutic plan, the Medication Regime Complexity Index.

Measures and Outcomes:

To measure the care burden, the Burden Scale for Family Caregiver was used and for the complexity of the therapeutic plan, the Medication Regime Complexity Index.

Results:

One hundred and forty patients were enrolled with their family caregivers: patients with nononcological pathologies (n = 63) and patients with cancer (n = 77). Caregiver's burden score is statistically significantly correlated with the complexity of the medical plan in both groups (P = 0.32 and P = 0.012 respectively). The average family caregiver's burden was significantly higher in the nononcological group (45 ± 14.45 vs. 36.52 ± 15.05; P = 0.001). The number of medications that family caregivers administer daily for patients without cancer is higher than in the other subset (8.25 ± 4.94 vs. 5.89 ± 4.93; P = 0.004). Opioids were more frequently used for pain control in cancer patients (5 vs. 72; P = 0.0001).

Conclusions:

The caregiver's burden is high for nononcological patients. The complexity of the treatment plan (number of drugs and frequency of administration) is significantly correlated with the care burden. Further studies are needed to understand which interventions targeted on family caregivers will minimize the burden of care.
Fertility preservation in uro-oncology
Authors: Moore Kieran J. , Delgado Carlos , Ory Jesse
Published: November 2022

Purpose of review

The purpose of this review is to highlight the demand for fertility preservation among cancer survivors and to draw attention to areas where healthcare workers need to improve. As technology advances, maximizing cryopreservation rates will be paramount to increase the ability individuals to conceive after cancer treatment.

Recent findings

Guidelines recommending discussion of fertility for those diagnosed with cancer have been shown to increase patient satisfaction and overall quality of life. Our review demonstrated that increasing counseling rates remains an ongoing challenge and should remain an area of improvement for all healthcare professionals working in the oncology field. Formal programs to improve patient and provider education and access to fertility preservation increase uptake of fertility preservation. For men, many options exist to cryopreserve sperm; a slight delay to achieve fertility preservation has not been shown to lead to worse outcomes. Cryopreservation strategies differ based on puberty status and remain an active area of clinical research.

Improving fertility outcomes for cancer survivors is possible with appropriate counseling techniques at the time of cancer diagnosis. Clinicians should challenge current barriers for patient access to fertility preservation surrounding cancer treatments.
Mothers modify the cost of reproduction by dynamic changes in antioxidant function and filial cannibalism
Authors: Sawecki Jake , Dijkstra Peter D.
Published: November 2022

Investment in current reproduction may negatively influence subsequent fitness. Oxidative stress has been proposed as a potential mediator of this trade-off between current and future reproductive success. However, evidence of reproduction causing oxidative stress is limited, possibly owing to compensatory mechanisms that counteract oxidative insults. Here we test the idea that organisms protect against oxidative challenges through a dynamic interaction between behavioural and physiological adjustments at different stages of reproduction. To test this idea, we manipulated maternal care in the mouthbrooding cichlid fish
Astatotilapia burtoni
by allowing females to continue care (brooders) or by preventing care (non-brooders). We found that brooders depleted the pool of antioxidants as brood care progressed; however, we only observed increased oxidative DNA damage at the early stage of care relative to non-brooders, possibly owing to upregulated antioxidant protection during later stages of care. Most brooders adjusted parental investment by consuming some of their offspring during mouthbrooding. Intriguingly, the level of filial cannibalism was positively related to liver antioxidant function. These changes in antioxidant function and filial cannibalism allow parents to manage the cost of reproduction and are important for our understanding of how oxidative stress mediates life-history trade-offs.
Why are cell populations maintained via multiple compartments?
Authors: Feliciangeli Flavia , Dreiwi Hanan , López-García Martín , Castro Ponce Mario , Molina-París Carmen , Lythe Grant
Published: November 2022

We consider the maintenance of ‘product’ cell populations from ‘progenitor’ cells via a sequence of one or more cell types, or compartments, where each cell’s fate is chosen stochastically. If there is only one compartment then large amplification, that is, a large ratio of product cells to progenitors comes with disadvantages. The product cell population is dominated by large families (cells descended from the same progenitor) and many generations separate, on average, product cells from progenitors. These disadvantages are avoided using suitably constructed sequences of compartments: the amplification factor of a sequence is the product of the amplification factors of each compartment, while the average number of generations is a sum over contributions from each compartment. Passing through multiple compartments is, in fact, an efficient way to maintain a product cell population from a small flux of progenitors, avoiding excessive clonality and minimizing the number of rounds of divisionen route. We use division, exit and death rates, estimated from measurements of single-positive thymocytes, to choose illustrative parameter values in the single-compartment case. We also consider a five-compartment model of thymocyte differentiation, from double-negative precursors to single-positive product cells.
IL-33-induced neutrophilic inflammation and NETosis underlie rhinovirus-triggered exacerbations of asthma
Authors: Curren Bodie , Ahmed Tufael , Howard Daniel R , Ullah Md. Ashik , Sebina Ismail , Rashid Ridwan B , Sikder Md. Al Amin , Bissell Alec , Ngo Sylvia , Jackson David J , Toussaint Marie , Edwards Michael R. , Johnston Sebastian L , McSorley Henry J. , Phipps Simon
Published: November 2022

Rhinovirus-induced neutrophil extracellular traps (NETs) contribute to acute asthma exacerbations, however the molecular factors that trigger NETosis in this context remain ill-defined. Here, we sought to implicate a role for IL-33, an epithelial cell-derived alarmin rapidly released in response to infection. In mice with chronic experimental asthma (CEA), but not naïve controls, rhinovirus inoculation induced an early (1 day post infection; dpi) inflammatory response dominated by neutrophils, neutrophil-associated cytokines (IL-1α, IL-1β, CXCL1) and NETosis, followed by a later, type-2 inflammatory phase (3-7 dpi), characterized by eosinophils, elevated IL-4 levels, and goblet cell hyperplasia. Notably, both phases were ablated by HpARI (Heligmosomoides polygyrusAlarmin Release Inhibitor), which blocks IL-33 release and signalling. Instillation of exogenous IL-33 recapitulated the rhinovirus-induced early phase, including the increased presence of NETs in the airway mucosa, in a PAD4-dependent manner.Ex vivoIL-33-stimulated neutrophils from mice with CEA, but not naïve mice, underwent NETosis, and produced greater amounts of IL-1α/β, IL-4, and IL-5. In nasal samples from rhinovirus-infected people with asthma, but not healthy controls, IL-33 levels correlated with neutrophil elastase and dsDNA. Our findings suggest that IL-33 blockade ameliorates the severity of an asthma exacerbation by attenuating neutrophil recruitment and the downstream generation of NETs.
Optimization of the Illumina COVIDSeq™protocol for decentralized, cost-effective genomic surveillance
Authors: Carpenter Rob E. , Tamrakar Vaibhav K. , Almas Sadia , Rowan Chase , Sharma Rahul
Published: November 2022

A decentralized surveillance system to identify local outbreaks and monitor SARS-CoV-2 Variants of Concern is one of the primary strategies for the pandemic’s containment. Although next-generation sequencing (NGS) is a gold standard for genomic surveillance and variant discovery, the technology is still cost-prohibitive for decentralized sequencing, particularly in small independent labs with limited resources. We have optimized the Illumina COVID-seq protocol to reduce cost without compromising accuracy. 90% of genomic coverage was achieved for 142/153 samples analyzed in this study. The lineage was correctly assigned to all samples (152/153) except for one. This modified protocol can help laboratories with constrained resources contribute to decentralized SARS-CoV-2 surveillance in the post-vaccination era.
Western Washington culvert prioritization indexes: A cross jurisdictional comparative analysis of management strategies for salmon recovery
Authors: Burch Catalina A. , Jardine Sunny L. , Lewis-Smith Connor , Van Deynze Braeden
Published: November 2022

Culverts throughout western Washington state, U.S.A., contribute to declines in anadromous fish populations by blocking fish passage. A federal injunction requires that Washington state must restore 90 percent of blocked habitat caused by state-owned culverts by 2030. This ruling prompted the development of numerous prioritization indexes (PI), the ranking of barriers through weighted combinations of barrier-specific metrics, by culvert owning entities (i.e., counties, cities, ect.) within the injunction area. We conduct a comparative analysis of PIs within the injunction case area, investigating their ability to distinguish between barriers, their transferability in terms of scoring metrics utilized, how scoring weights differ, and the preferences implied thereby. We document the use of six distinct PI methods by ten barrier owning entities, and find that some PIs used many shared metrics, while others used a high percentage of unique metrics that would be difficult to replicate outside the entity’s jurisdiction. While habitat quality, habitat quantity, and connectivity were considered across all PIs, we found a high level of variation in terms of the metric weights. Our methods can be employed in other geographies or for other restoration PI planning efforts, and our results may facilitate the development and refinement of future PIs.
Mapping human social brain specialisation beyond the neuron using multimodal imaging in human infants
Authors: Siddiqui Maheen , Pinti Paola , Brigadoi Sabrina , Lloyd-Fox Sarah , Elwell Clare E. , Johnson Mark H. , Tachtsidis Ilias , Jones Emily J.H.
Published: November 2022

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of this process is based on evidence from unitary imaging modalities and has thus focused on isolated changes in spatial or temporal precision of neural or haemodynamic activation alone, giving an incomplete picture of the process. We speculate that neural specialisation of function will be underpinned by better coordinated haemodynamic and metabolic changes in a broader orchestrated physiological response. Thus, we present a harmonised framework in which specialisation is indexed by the emergence of coupling between neuronal activity and vascular supply of oxygen and energy. Here, we combine simultaneous measures of coordinated neural activity (EEG), metabolic rate and oxygenated blood supply (broadband near-infrared spectroscopy) to measure emerging specialisation in the infant brain. In 4-to-7-month-old infants, we show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high frequency brain activity. We conclude that functional specialisation of the brain is a coordinated activity across neural, haemodynamic, and metabolic changes, and our ability to measure these simultaneously opens new vistas in understanding how the brain is shaped by its environment.
Nucleosome sensitivity distinguishes colon polyps based on their transformation status
Authors: Khadem Mahdi , Kossick Kimberlee , Fedyshyn Yaroslav , Boardman Lisa , Dennis Jonathan H. , Druliner Brooke R.
Published: November 2022

One of the keys to eliminating the personal and financial costs of cancer lies in the early detection of the disease. Consequently, effective cancer interventions increasingly rely on our understanding of the earliest cellular and nuclear events that lead to oncogenic transformation. Colorectal cancer, the third most prevalent cancer in the United States, results from the transformation of polyps. Our group demonstrated that the alteration of chromatin organization is a pivotal event in this oncogenic transformation. Here, we analyze the differences of the nucleosomal sensitivity to mocroccocal nuclease (MNase) between histopathologically matched pre-cancerous polyps taken from patients that did not develop cancer (cancer-free polyps, CFP) and those that did develop cancer (cancer-associated polyps, CAP). We produced high-resolution nucleosome distribution and nucleosome sensitivity maps from each of the five CFP patient samples and three CAP patient samples. We show that nucleosome distribution is largely invariant between CFP and CAP samples. Nucleosome sensitivity, however, is a powerful analysis that can identify genomic locations that distinguish CFP from CAP. We have identified more than 1000 genomic locations with altered nucleosomal sensitivity that discriminate between CAP and CFP. Furthermore, we show that these genomic locations with altered nucleosomal sensitivity between CFP and CAP include genes that play critical roles in oncogenic transformation. We propose that nucleosome sensitivity serves as a robust biomarker indicating the oncogenic potential of precancerous polyps and could be used for the early detection of polyps that will become cancerous.
The microtubular preprophase band recruits Myosin XI to the division site for plant cytokinesis
Authors: Huang Calvin Haoyuan , Peng Felicia Lei , Lee Yuh-Ru Julie , Liu Bo
Published: November 2022

Plant growth is dependent on oriented cell divisions that employ the microtubular preprophase band (PPB) to position the cell plate. It has been intriguing how this transient cytoskeletal array imprints the spatial information to be read by the cytokinetic phragmoplast at later stages of mitotic cell division. InArabidopsis thaliana, we discovered that the PPB recruited the Myosin XI motor MYA1 to the cortical division site where it joined microtubule-associated proteins and motors to form a ring of prominent cytoskeletal assemblies which received the expanding phragmoplast. This regulatory function of MYA1 in phragmoplast guidance is dependent on intact actin filaments. The discovery of these assemblies revealed the mechanism underlying how two dynamic cytoskeletal networks govern PPB-dependent division plane orientation during vegetative growth in flowering plants.

ONE-SENTENCE SUMMARY

Myosin XI joins microtubule-associated proteins and motors to form cortical assemblies to demarcate the cell division site.
Control ofClostridiodes difficilevirulence and physiology by the flagellin homeostasis checkpoint FliC-FliW-CsrA in the absence of motility
Authors: Zhu Duolong , Wozniak Katherine J. , Midani Firas , Wang Shaohui , Sun Xingmin , Britton Robert A.
Published: November 2022

Mutations affectingClostridioides difficileflagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involvingfliC,fliW, andcsrA, which creates a feedback system to regulate flagella production. Through genomic analysis ofC. difficileclade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin genefliCand regulatory genefliW. We therefore investigated the roles offliC,fliW, andcsrAin the clade 5 ribotype 078 strainC. difficile1015, which lacks flagella and is non-motile. Analysis of mutations infliC,fliW, andcsrA(and all combinations) onC. difficilepathogenesis indicated that FliW plays a central role inC. difficilevirulence as animals infected with strains carrying a deletion offliWshowed decreased survival and increased disease severity. Thesein vivofindings were supported byin vitrostudies showing that mutations impacting the activity of FliW showed increased toxin production. We further identified that FliW can interact with the toxin positive regulator TcdR, indicating that modulation of toxin production via FliW occurs by sequestering TcdR from activating toxin transcription. Furthermore, disruption of thefliC-fliW-csrAnetwork results in significant changes in carbon source utilization and sporulation. This work highlights that key proteins involved in flagellar biosynthesis retain their regulatory roles inC. difficilepathogenesis and physiology independent of their functions in motility.

IMPORTANCE

C. difficileis a leading cause of nosocomial antibiotic-associated diarrhea in developed countries with many known virulence factors. In several pathogens, motility and virulence are intimately linked by regulatory networks that allow coordination of these processes in pathogenesis and physiology. Regulation ofC. difficletoxin production by FliC has been demonstratedin vitroandin vivoand has been proposed to link motility and virulence. Here we show that clinically important, non-motileC. difficilestrains have conserved FliC and regulatory partners FliW and CsrA, despite lacking the rest of the machinery to produce functional flagella. Our work highlights a novel role for flagellin outside of its role in motility and FliW in the pathogenesis and physiology ofC. difficile.
scmTE: multivariate transfer entropy builds interpretable compact gene regulatory networks by reducing false predictions
Authors: Weng Guangzheng , Kim Junil , Natarajan Kedar Nath , Won Kyoung-Jae
Published: November 2022

Gene regulatory network inference from single-cell RNA sequencing (scRNAseq) datasets has an incredible potential to discover new regulatory rules. However, current computational inference methods often suffer from excessive predictions as existing strategies fail to remove indirect or false predictions. Here, we report a new algorithm single-cell multivariate Transfer Entropy, ‘scmTE’, that generates interpretable regulatory networks with reduced indirect and false predictions. By utilizing multivariate transfer entropy, scmTE accounts for gene-to-gene interdependence when quantifying regulatory relationships. Benchmarking against other methods using synthetic data manifested that scmTE is the unique algorithm that did not produce a hair-ball structure (due to too many predictions) and recapitulated known ground-truth relationships with high accuracy.In silicoknockdown experiments shows that scmTE assigns higher scores for specific interactions important for differentiation processes. We apply scmTE to T-cell differentiation, myelopoiesis and pancreatic development and identified known and novel regulatory interactions. scmTE provides a robust approach to infer interpretable networks by effectively removing unwanted indirect relationships.
SSB toolkit: from molecular structure to subcellular signaling pathways
Authors: Ribeiro Rui Pedro , Goßen Jonas , Rossetti Giulia , Giorgetti Alejandro
Published: November 2022

We present, here, an open-source systems biology toolkit to simulate mathematical models of the signal-transduction pathways of G-protein coupled receptors (GPCRs). By merging structural macromolecular data with systems biology simulations, we developed a framework to simulate the signal-transduction kinetics induced by ligand-GPCR interactions, as well as the consequent change of concentration of signaling molecular species, as a function of time and ligand concentration. Therefore, this tool brings to the light the possibility to investigate the subcellular effects of ligand binding upon receptor activation, deepening the understanding of the relationship between the molecular level of ligand-target interactions and higher-level cellular and physiologic or pathological response mechanisms.
Functional differentiation of Sec13 paralogs in the euglenozoan protists
Authors: Faktorová Drahomíra , Záhonová Kristína , Benz Corinna , Dacks Joel B. , Field Mark C. , Lukeš Julius
Published: November 2022

The β-propeller protein Sec13 plays roles in at least three distinct processes by virtue of being a component of the COPII endoplasmic reticulum export vesicle coat, the nuclear pore complex (NPC) and the Seh1-associated (SEA)/GATOR nutrient-sensing complex, suggesting that regulatory mechanisms coordinating these cellular activities may operateviaSec13. The NPC, COPII and SEA/GATOR are all ancient features of eukaryotic cells. In the vast majority of eukaryotes, a single Sec13 gene is present, but here we report that the Euglenozoa, a lineage encompassing the diplonemid, kinetoplastid and euglenid protists contain two Sec13 paralogs. Furthermore, based on protein interactions and localization studies we show that Sec13 functions in diplonemids are divided between the Sec13a and Sec13b paralogs. Specifically, Sec13a interacts with COPII and the NPC, but Sec13b interacts with Sec16 and components of the SEA/GATOR complex. We infer that euglenozoan Sec13a is responsible for NPC functions and canonical anterograde transport activities while Sec13b acts within nutrient and autophagy-related pathways, indicating a fundamentally distinct organization of coatomer complexes in the euglenozoan flagellates.
Membrane-remodeling protein ESCRT-III homologs incarnate the evolution and morphogenesis of multicellular magnetotactic bacteria
Authors: Zhang Wenyan , Chen Jianwei , Dai Jie , Zhu Shiwei , Guenno Hugo Le , Kosta Artemis , Pan Hongmiao , Qian Xin-Xin , Santini Claire-Lise , Menguy Nicolas , Li Xuegong , Chen Yiran , Liu Jia , Cui Kaixuan , Zhao Yicong , Liu Guilin , Durand Eric , Zhang Wei-Jia , Roussel Alain , Xiao Tian , Wu Long-Fei
Published: November 2022

Endosomal sorting complex required transport (ESCRT) III proteins are essential for membrane remodeling and repair across all domains of life. Eukaryotic ESCRT-III and the cyanobacterial homologs PspA and Vipp1/Imm30 remodel membrane into vesicles, rings, filaments and tubular rods structures. Here our microscopy analysis showed that multicellular bacteria, referred to as magnetoglobules, possess multiple compartments including magnetosome organelles, polyphosphate granules, vesicles, rings, tubular rods, filaments and MVB-like structures. Therefore, membrane remodeling protein PspA might be required for the formation of these compartments, and contribute to the morphogenesis and evolution of multicellularity. To assess these hypotheses, we sequenced nine genomes of magnetoglobules and found a significant genome expansion compared to unicellular magnetotactic bacteria. Moreover, PspA was ubiquitous in magnetoglobules and formed a distinct clade on the tree of eubacterial and archaeal ESCRT-III. The phylogenetic feature suggested the evolution of magnetoglobules from a unicellular ancestor of deltaproteobacterium. Hetero-expression of ellipsoidal magnetoglobulepspA2gene alone inEscherichia coliresulted in intracellular membrane aggregation. GFP fusion labeling revealed polar location of PspA2 in rod-shaped unicells and regular interval location in filamentous cells. Cryo-electron tomography analysis showed filament bundle, membrane sacculus, vesicles and MVB-like structure in the cells expressing PspA2. Moreover, electron-dense area with a similar distribution as GFP-PspA2 foci in filamentous cells changed the inward orientation of the septum, which might interfere with the cell division. Collectively, these results show the membrane remodeling function of magnetoglobule PspA proteins, which may contribute to morphogenesis and the evolution of multicellularity of magnetotactic bacteria.
Potassium regulates axon-oligodendrocyte signaling and metabolic coupling in white matter
Authors: Looser Zoe J. , Ravotto Luca , Jung Ramona B. , Werner Hauke B. , Ruhwedel Torben , Möbius Wiebke , Bergles Dwight E. , Barros L. Felipe , Nave Klaus-Armin , Weber Bruno , Saab Aiman S.
Published: November 2022

The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs), which is essential for brain function. However, the mechanisms by which OLs detect axonal spiking and rapidly control axon-OL metabolic coupling are largely unknown. Here, we combine optic nerve electrophysiology and two-photon imaging to study activity-dependent calcium (Ca2+) dynamics in OLs and metabolite fluxes in myelinated axons. Both high-frequency axonal firing and extracellular potassium (K+) elevations trigger a fast Ca2+response in OLs that is facilitated by barium-sensitive, inwardly rectifying K+channels. Using OL-specific Kir4.1 knockout mice (Kir4.1 cKO) we now demonstrate that, in addition to being crucial for K+clearance, oligodendroglial Kir4.1 regulates axonal energy metabolism and long-term axonal integrity. Before the manifestation of axonal damage, we observed reduced glucose transporter GLUT1 and monocarboxylate transporter MCT1 expression in myelin of young Kir4.1 cKO mice, suggesting early deficits in metabolite supply to axons. Strikingly, we found lower resting lactate levels and activity-induced lactate surges in optic nerve axons of young Kir4.1 cKO mice. Moreover, both axonal glucose uptake and consumption were hampered in the absence of oligodendroglial Kir4.1, uncovering a new role of OLs in regulating axonal glucose metabolism. Our findings reveal a novel model of axon-OL signaling and metabolic coupling in which OLs detect high-frequency axonal activity through K+signaling, which is critical in adjusting the axon-OL metabolic unit and in preserving long-term axonal health.
Sensory tuning in neuronal movement commands
Authors: Baumann Matthias P. , Bogadhi Amarender R. , Denninger Anna F. , Hafed Ziad M.
Published: November 2022

Movement control is critical for successful interaction with our environment. However, movement does not occur in complete isolation of sensation, and this is particularly true of eye movements. Here we show that the neuronal eye movement commands emitted by the superior colliculus, a structure classically associated with oculomotor control, encompass a robust visual sensory representation of eye movement targets. Thus, similar saccades towards different images are associated with different saccade-related “motor” bursts. Such sensory tuning in superior colliculus saccade motor commands appeared for all image manipulations that we tested, from simple visual features to real-life object images, and it was also strongest in the most motor neurons in the deeper collicular layers. Visual-feature discrimination performance in the motor commands was also stronger than in visual responses. Comparing superior colliculus motor command feature discrimination performance to that in the primary visual cortex during steady gaze fixation revealed that collicular motor bursts possess a reliable peri-saccadic sensory representation of the peripheral saccade target’s visual appearance, exactly when retinal input is most uncertain. Consistent with this, we found that peri-saccadic perception is altered as a function of saccade target visual features. Therefore, superior colliculus neuronal movement commands likely serve a fundamentally sensory function.