bluuebunny/crossref_metadata_2025 huggingface dataset:
Dead-Space Ventilation Indices and Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis*
Authors: Jayasimhan Dilip , Chieng Jennifer , Kolbe John , Sidebotham David A.
Published: May 2023

OBJECTIVES:

Acute respiratory distress syndrome (ARDS) is associated with high ventilation-perfusion heterogeneity and dead-space ventilation. However, whether the degree of dead-space ventilation is associated with outcomes is uncertain. In this systematic review and meta-analysis, we evaluated the ability of dead-space ventilation measures to predict mortality in patients with ARDS.

DATA SOURCES:

MEDLINE, CENTRAL, and Google Scholar from inception to November 2022.

STUDY SELECTION:

Studies including adults with ARDS reporting a dead-space ventilation index and mortality.

DATA EXTRACTION:

Two reviewers independently identified eligible studies and extracted data. We calculated pooled effect estimates using a random effects model for both adjusted and unadjusted results. The quality and strength of evidence were assessed using the Quality in Prognostic Studies and Grading of Recommendations, Assessment, Development, and Evaluation, respectively.

DATA SYNTHESIS:

We included 28 studies in our review, 21 of which were included in our meta-analysis. All studies had a low risk of bias. A high pulmonary dead-space fraction was associated with increased mortality (odds ratio [OR], 3.52; 95% CI, 2.22–5.58; p < 0.001; I
2 = 84%). After adjusting for other confounding variables, every 0.05 increase in pulmonary-dead space fraction was associated with an increased odds of death (OR, 1.23; 95% CI, 1.13–1.34; p < 0.001; I
2 = 57%). A high ventilatory ratio was also associated with increased mortality (OR, 1.55; 95% CI, 1.33–1.80; p < 0.001; I
2 = 48%). This association was independent of common confounding variables (OR, 1.33; 95% CI, 1.12–1.58; p = 0.001; I
2 = 66%).

CONCLUSIONS:

Dead-space ventilation indices were independently associated with mortality in adults with ARDS. These indices could be incorporated into clinical trials and used to identify patients who could benefit from early institution of adjunctive therapies. The cut-offs identified in this study should be prospectively validated.
Special Issues in Adolescent Medicine: Medical and Legal Aspects of Care in Adolescent Medicine
Authors: Swedler Jane , Alderman Elizabeth M.
Published: May 2023

Providing medical care and managing the health care needs of adolescents can be a complex process. Knowing, which adolescents can consent to health care and the scope of services adolescents can consent to, what information can be kept confidential and from whom, under which circumstances information must be disclosed, and how to navigate parental involvement, is vital for the practice of adolescent medicine. This chapter aims to address some of these issues and assist health care providers in gaining knowledge and expertise in the optimal delivery of care for adolescents.
Improving Health Care Responses to Obstetric Hemorrhage
Authors: Schneider Patrick
Published: May 2023

Obstetric hemorrhage is one of the most commonly encountered obstetrical complications. Decreases in maternal mortality and severe maternal morbidity have continued to be achieved despite the increasing incidence of obstetric hemorrhage over time through the diligent efforts of quality improvement initiatives. Approaches currently advocated to optimize the management of obstetrical hemorrhage are presented and discussed in this chapter focusing on readiness, recognition and prevention, clinical response, patient support, and tracking and monitoring outcome and performance measures over time. Readers are encouraged to access publicly available programs from state-based perinatal quality collaboratives and national programs designed to support and structure such efforts.
Neoadjuvant Immune Checkpoint Inhibition in Metastatic Conjunctival Melanoma
Authors: Fan Kelly , Waninger Jessica J. , Yentz Sarah , McLean Scott , Demirci Hakan
Published: May 2023

The development of immune checkpoint inhibitors (ICI) has transformed the treatment of advanced-stage cutaneous melanoma; however, most trials did not include patients with conjunctival melanoma. Herein the authors describe a patient with recurrent conjunctival melanoma who developed locally advanced, b-raf and v-raf murine sarcoma viral oncogene homolog B1-negative melanoma in her nasal cavity and extensive, metabolically active, bilateral lymphadenopathy in her thorax. Her nasal mass measured 4.3 × 1.7 cm and was determined to be unresectable. She was treated with 4 cycles of combination ipilimumab and nivolumab therapy followed by maintenance nivolumab. She experienced a dramatic treatment response with a reduction in the size of her nasal mass to 3.0 × 1.1 cm and a complete resolution of her adenopathy. She then underwent complete surgical resection of her residual mass (approximately 75% of her original tumor size) and remains melanoma-free at 1 year of follow-up. Given the underlying genetic similarities of conjunctival melanoma to cutaneous melanoma, providers should consider the use of neoadjuvant immune checkpoint inhibitors for patients with locally advanced or limited metastatic disease.
A Mixed-Methods Study of Social Determinants and Self-care in Adults With Heart Failure
Authors: Osei Baah Foster , Brawner Bridgette M. , Teitelman Anne M. , Ruger Jennifer Prah , Riegel Barbara
Published: May 2023

Background

The burden of heart failure (HF) is unequally distributed among population groups. Few study authors have described social determinants of health (SDoH) enabling/impeding self-care.

Aim

The aim of this study was to explore the relationship between SDoH and self-care in patients with HF.

Methods

Using a convergent mixed-methods design, we assessed SDoH and self-care in 104 patients with HF using the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE) and the Self-Care of HF Index v7.2 with self-care maintenance, symptom perception, and self-care management scales. Multiple regression was used to assess the relationship between SDoH and self-care. One-on-one in-depth interviews were conducted in patients with poor (standardized score ≤ 60, n = 17) or excellent (standardized score ≥ 80, n = 20) self-care maintenance. Quantitative and qualitative results were integrated.

Results

Participants were predominantly male (57.7%), with a mean age of 62.4 ± 11.6 years, with health insurance (91.4%) and some college education (62%). Half were White (50%), many were married (43%), and most reported adequate income (53%). The money and resources core domain of PRAPARE significantly predicted self-care maintenance (P = .019), and symptom perception (P = .049) trended significantly after adjusting for other PRAPARE core domains (personal characteristics, family and home, and social and emotional health) and comorbidity. Participants discussed social connectedness, health insurance coverage, individual upbringing, and personal experiences as facilitators of self-care behavior.

Conclusion

Several SDoH influence HF self-care. Patient-specific interventions that address the broader effects of these factors may promote self-care in patients with HF.
Automated diagnosis and management of follicular thyroid nodules based on the devised small-datasets interpretable foreground optimization network deep learning: A multicenter diagnostic study
Authors: Yang Zheyu , Yao Siqiong , Heng Yu , Shen Pengcheng , Lv Tian , Feng Siqi , Tao Lei , Zhang Weituo , Qiu Weihua , Lu Hui , Cai Wei
Published: May 2023

Background:

Currently, follicular thyroid carcinoma (FTC) has relatively low incidence with a lack of effective preoperative diagnostic means. To reduce the need for diagnostic invasive procedures and to address information deficiencies inherent in a small-dataset, we utilized interpretable foreground optimization network deep learning to develop a reliable preoperative FTC detection system.

Methods:

In this study, a deep learning model (FThyNet) was established using preoperative ultrasound images. Data on patients in training and internal validation cohort (n=432) were obtained from XXX Hospital, China. Data on patients in external validation cohort (n=71) were obtained from four other clinical centers. We evaluated the predictive performance of FThyNet and its ability to generalize across multiple external centers and compared the results yielded with assessments from physicians directly predicting FTC outcomes. In addition, the influence of texture information around the nodule edge on the prediction results was evaluated.

Results:

FThyNet had a consistently high accuracy in predicting FTC with area under the receiver operating characteristic curve (AUC) of (89.0% [95% CI 87.0-90.9]). Particularly, the AUC for grossly invasive-FTC reached 90.3%, which was significantly higher than that of the radiologists (56.1% [95% CI 51.8-60.3]). The parametric visualization study found that those nodules with blurred edges and relatively distorted surrounding textures were more likely to have FTC. Furthermore, edge texture information played an important role in FTC prediction with an AUC of (68.3% [95% CI 61.5–75.5]), and highly invasive malignancies had the highest texture complexity.

Conclusion:

FThyNet could effectively predict FTC, provide explanations consistent with pathological knowledge, and improve clinical understanding of the disease.
Impact of Anticholinergic Medications on Speech Perception Performance after Cochlear Implantation
Authors: Layfield Eleanor , Hwa Tiffany Peng , Quimby Alexandra E. , Brant Jason A. , Bigelow Douglas , Ruckenstein Michael J. , Eliades Steven J.
Published: May 2023

Objective

To identify and characterize the impact of anticholinergic medications, which have known adverse effects on cognition in older adults, on speech perception after cochlear implantation.

Study Design

Retrospective cohort.

Setting

Tertiary referral center.

Subject Population

Adult patients who underwent cochlear implantation between January 2010 and September 2020 with speech perception scores at 3, 6, and 12 months.

Interventions

Anticholinergic burden of patients' prescribed medications.

Main Outcome Measures

AzBio speech perception scores after implantation.

Results

One hundred twenty-six patients had documented AzBio in quiet speech perception score at all three postactivation time points. Patients were divided into three groups by anticholinergic burden (ACB) score, including ACB = 0 (90 patients), 1 (23 patients), and ≥2 (13 patients). There was no statistically significant difference between ACB groups in audiologic performance at candidacy testing (p = 0.77) or at 3 months after implantation (p = 0.13). Beginning at 6 months, a lower mean AzBio was seen in patients with higher ACB scores (68% ACB = 0; 62% ACB = 1; 48.1% ACB ≥ 2; p = 0.03). At 12 months, there were further differences between the groups (71.0% ACB = 0, 69.5% ACB = 1, 48.0% ACB ≥2, p < 0.01). Controlling for the effects of age using multivariate linear regression showed persistent effects of ACB score on learning-related AzBio improvements. Comparatively, the negative impact of a single ACB score point was equivalent to nearly 10 years of aging (p = 0.03).

Conclusions

Increased ACB is associated with worse speech perception scores after cochlear implantation, an effect that persists even when accounting for patient age, suggesting that these medications may have cognitive and learning effects that reduce cochlear implant performance.
Gluten Immunogenic Peptides Are Not Correlated With Reported Adherence to Gluten-Free Diet in Children With Celiac Disease
Authors: Guz-Mark Anat , Perets Tsachi Tsadok , Biran Neta , Jack Yifat , Zevit Noam , Silbermintz Ari , Matar Manar , Nachmias-Friedler Vered , Waisbourd-Zinman Orith , Bar-Lev Michal Rozenfeld , Huta Yair , Ashorov Olga , Gingold-Belfer Rachel , Shamir Raanan
Published: May 2023

Objective:

There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence.

Methods:

Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis.

Results:

The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8–11.7) years, and median (IQR) duration on GFD of 2.5 (2–5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms.

Conclusions:

Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.
Social Determinants of Health Are Associated With Visits for Ambulatory Care Sensitive Conditions
Authors: Das Kristol , Onwuka Amanda J. , Chisolm Deena J.
Published: May 2023

Objectives

Population health experts have described the link between social factors and health, but few studies link specific social needs to disease processes. Nationwide Children's Hospital implemented a universal, annual screener for social determinants of health (SDH) in 2018. Early analyses have shown that patients identifying an SDH need were more likely to have an emergency department (ED) or inpatient stay. The objective of this study is to identify links between SDH and ED presentation for ambulatory care sensitive conditions (ACSCs).

Methods

This was a retrospective observational study of children aged 0–21 years receiving care at Nationwide Children's Hospital from 2018 to 2021 that were screened for SDH. Acute care utilization within 6 months of screener completion, sociodemographic, and clinical data were collected via EPIC data extraction. Patients that completed screening tool for the first time in the ED were excluded to minimize selection bias. Logistic regression was used to analyze the association between ED presentation for ACSCs and SDH needs.

Results

A total of 108,346 social determinants screeners were included with 9% of screeners identifying a need. Five percent of the population expressed food needs, 4% transportation needs, 3% utility needs, and 1% housing needs. Eighteen percent of patients had an ED visit for ACSC, with the most common complaints being upper respiratory infections and asthma. Having any SDH need was associated with ED visits for ACSCs (odds ratio, 1.12; 95% confidence interval, 1.06–1.18). Needs in all domains were significantly associated with increased visits for ACSCs; however, patients with housing needs had the highest odds of utilization (odds ratio, 1.25; confidence interval, 1.11–1.41).

Conclusions

The odds of ED presentation for ACSCs are higher in patients with expressed social needs. Further delineating the connections between specific SDH and health outcomes can inform timely and appropriate interventions.
Closing the Loop
Authors: McGahern Candice , Cantor Zachary , De Mendonca Benjamin , Dawson Jennifer , Boisvert Liane , Dalgleish Dale , Newhook Dennis , Reddy Deepti , Bresee Natalie , Alnaji Fuad
Published: May 2023

Objectives

Providing emergency care to acutely ill or injured children is stressful and requires a high level of training. Paramedics who provide prehospital care are typically not involved in the circle of care and do not receive patient outcome information. The aim of this quality improvement project was to assess paramedics' perceptions of standardized outcome letters pertaining to acute pediatric patients that they had treated and transported to an emergency department.

Methods

Between December 2019 and December 2020, 888 outcome letters were distributed to paramedics who provided care for 370 acute pediatric patients transported to the Children's Hospital of Eastern Ontario in Ottawa, Canada. All paramedics who received a letter (n = 470) were invited to participate in a survey that collected their perceptions and feedback about the letters, as well as their demographic information.

Results

The response rate was 37% (172/470). Approximately half of the respondents were Primary Care Paramedics and half Advanced Care Paramedics. The respondents' median age was 36 years, median years of service was 12 years, and 64% identified as male. Most agreed that the outcome letters contained information pertinent to their practice (91%), allowed them to reflect on care they had provided (87%), and confirmed clinical suspicions (93%). Respondents indicated that they found the letters useful for 3 reasons: 1) increases capacity to link differential diagnoses, prehospital care, or patient outcomes; 2) contributes to a culture of continuous learning and improvement; and 3) gives closure, reduces stress, or provides answers for difficult cases. Suggestions for improvement included providing more information, provision of letters on all patients transported, faster turnaround time between call and receipt of letter and inclusion of recommendations or interventions/assessments.

Conclusions

Paramedics appreciated receiving hospital-based patient outcome information after their provision of care and reported that the letters offered opportunities for closure, reflection, and learning.
Clinical Efficiency of High-Intensity Laser Therapy in Patients With Cervical Radiculopathy
Authors: İnce Songül , Eyvaz Nuran , Dündar Ümit , Toktaş Hasan , Yeşil Hilal , Eroğlu Selma , Adar Sevda
Published: May 2023

Objective

The purpose of this study was to research the clinical effectiveness of high-intensity laser therapy combined with exercise on pain, quality of life, and disability in patients with cervical radiculopathy and compared it with that of placebo and exercise alone.

Design

Ninety participants with cervical radiculopathy were randomized into the following three groups: high-intensity laser therapy + exercise (n= 30), placebo + exercise (n= 30), and exercise only (n= 30). Pain, cervical range of motion, disability, and quality of life (36-item Short Form Health Survey) were assessed at baseline and weeks 4 and 12.

Results

The mean age of the patients (66.7% female) was 48.9 ± 9.3 yrs. Pain intensity in the arm and neck, neuropathic and radicular pain levels, disability, and several parameters of the 36-item Short Form Health Survey showed an improvement in the short and medium term in all three groups. These improvements were greater in the high-intensity laser therapy + exercise group than in the other two groups.

Conclusions

High-intensity laser therapy + exercise was much more effective in improving medium-term radicular pain, quality of life, and functionality in patients with cervical radiculopathy. Thus, high-intensity laser therapy should be considered for the management of cervical radiculopathy.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

At the conclusion of this article, readers will be able to: (1) Define cervical radicular pain and its clinical presentation, and explain the main pathomechanism in cervical radiculopathy (CR); (2) Describe the effects of laser administration on neuropathic pain; and (3) Discuss the clinical significance of coadministration of high-intensity laser therapy (HILT) with exercise (HILT + EX) in CR.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
The burden of cardiovascular risk in individuals with spinal cord injury (SCI) and its association with rehabilitation outcomes – Results from the Swiss SCI Cohort
Authors: Raguindin Peter Francis , Mueller Gabi , Stoyanov Jivko , Eriks-Hoogland Inge , Jordan Xavier , Stojic Stevan , Hund-Georgiadis Margret , Muka Taulant , Stucki Gerold , Glisic Marija ,   on behalf of the SwiSCI Study Group
Published: May 2023

Objectives

To determine the cardiovascular risk burden rehabilitation discharge, and explore the association between recovery during rehabilitation and CVD-risk profile

Methods

We included adults without CVD history admitted for rehabilitation. We evaluated rehabilitation outcomes on admission and discharge. CVD-risk was assessed by Framingham risk score (FRS), high-density lipoprotein (HDL), and fasting glucose level.

Results

We analyzed data from 706 participants (69.55% men) with median age of 53.5 years. The median time-since-injury was 14 days and the admission length was 5.2 months. Majority had paraplegia (53.26%), and motor incomplete injury (53.68%). One-third of the cohort had high cardiovascular risk profile pre-discharge. At discharge, poorer anthropometric measures were associated with higher FRS and lower HDL levels. Individuals with higher forced vital capacity (>2.72 L) and peak expiratory flow (>3.4 L/min) had 0.16 mmol/L and 0.14 mmol/L higher HDL compared to those with lower respiratory function, respectively. Individuals with higher mobility score (>12.5) and functional independence score (>74) had 0.21 mmol/L and 0.18 mmol/L higher HDL compared to those with lower scores.

Conclusion

There is high cardiometabolic syndrome burden and CVD-risk upon rehabilitation discharge. Higher respiratory function, mobility, and overall independence were associated with better CVD profile, although with study design limitations and short follow-up. Future studies should explore whether rehabilitation outcomes could be used to prioritize screening.
Predictors of Speech Language Pathology Referral Following Pediatric Concussion Using a Speech Language Checklist: A Brief Report
Authors: Oldham Jessie , Lent Barbara , Peretiatko Steven , Dec Katherine
Published: May 2023

Speech language pathologists (SLPs) have the training to treat pediatric concussion issues in communication; however, they have traditionally not been included in initial concussion treatment. Despite physician understanding of SLP engagement in traumatic brain injury, SLP referrals happen only after significant issues in returning to school occurred. Therefore, the purpose of this study was to investigate predictors of physician referral to SLP using an SLP screening checklist. This was a retrospective, cross-sectional study from an academic outpatient clinic. Our study included 60 concussion patients (57% female, 67% white, age: 18.3 ± 4.0 years) who were evaluated by specialist physicians. The independent variables include age, sex, and the speech screening checklist domains (attention, memory/organization, social interactions, word finding, executive function) and their associated subcategories. The primary study outcome was referral to SLP following concussion. Twenty-six patients (43%) were referred to SLP. The speech checklist domains significantly associated with a referral to SLP were attention and memory/organization. Individuals who reported trouble with attention or memory/organization on the speech language checklist were most likely to be referred in a concussion treatment plan. The use of a SLP checklist during patient visits may expedite referrals to SLP, achieve earlier therapeutic intervention, and facilitate recovery.
Characteristics of Associated Injuries in Children and Teenagers With Craniofacial Fractures
Authors: Kirvelä Aura , Snäll Johanna , Suominen Auli , Puolakkainen Tero , Thorén Hanna
Published: May 2023

The incidence of pediatric craniofacial fractures and heterogeneity of fractures is known to increase with age. This study aimed to determine the occurrence of associated injuries (AIs) to craniofacial fractures and identify differences in patterns of and predictors for AIs in children and teenagers. A 6-year retrospective cross-sectional cohort study was designed and implemented. The study population included 397 patients aged 19 years or less diagnosed with craniofacial fracture at Helsinki University Hospital from 2013 to 2018. Boys (71.0%) and teenagers (64.7%) were predominated. Associated injuries were more common in teenagers than children. Teenagers had more often AI in 2 or more organ systems. Assault and intoxication by alcohol were observed only in teenagers and predominantly boys. A total of 27.0% of all patients sustained AIs. In 18.1%, brain injury was reported. In children, motor vehicle accident (MVA) was an independent predictor for AI. In teenagers, independent predictors for AI were female sex, isolated cranial fracture, combined cranial fracture, and high-energy trauma mechanism. Injury patterns and AI related to craniofacial fractures in the pediatric population are age-specific, requiring multidisciplinary collaboration in the diagnosis, treatment, and follow-up of such trauma. Predictors for AIs increase in complexity with age, and the role of sex as a predictor is evident in teenagers.
Liproxstatin-1 Alleviates Lung Transplantation-induced Cold Ischemia–Reperfusion Injury by Inhibiting Ferroptosis
Authors: Zhao Jin , Li Jiawei , Wei Dong , Gao Fei , Yang Xiucheng , Yue Bingqing , Xiong Dian , Liu Mingzhao , Xu Hongyang , Hu Chunxiao , Chen Jingyu
Published: May 2023

Background.

Primary graft dysfunction, which is directly related to cold ischemia–reperfusion (CI/R) injury, is a major obstacle in lung transplantation (LTx). Ferroptosis, a novel mode of cell death elicited by iron-dependent lipid peroxidation, has been implicated in ischemic events. This study aimed to investigate the role of ferroptosis in LTx-CI/R injury and the effectiveness of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, in alleviating LTx-CI/R injury.

Methods.

LTx-CI/R-induced signal pathway alterations, tissue injury, cell death, inflammatory responses, and ferroptotic features were examined in human lung biopsies, the human bronchial epithelial (BEAS-2B) cells, and the mouse LTx-CI/R model (24-h CI/4-h R). The therapeutic efficacy of Lip-1 was explored and validated both in vitro and in vivo.

Results.

In human lung tissues, LTx-CI/R activated ferroptosis-related signaling pathway, increased the tissue iron content and lipid peroxidation accumulation, and altered key protein (GPX4, COX2, Nrf2, and SLC7A11) expression and mitochondrial morphology. In BEAS-2B cells, the hallmarks of ferroptosis were significantly evidenced at the setting of both CI and CI/R compared with the control, and the effect of adding Lip-1 only during CI was much better than that of only during reperfusion by Cell Counting Kit-8. Furthermore, Lip-1 administration during CI markedly relieved LTx-CI/R injury in mice, as indicated by significant improvement in lung pathological changes, pulmonary function, inflammation, and ferroptosis.

Conclusions.

This study revealed the existence of ferroptosis in the pathophysiology of LTx-CI/R injury. Using Lip-1 to inhibit ferroptosis during CI could ameliorate LTx-CI/R injury, suggesting that Lip-1 administration might be proposed as a new strategy for organ preservation.
Evaluation of the Modified Oxford Score in Recurrent IgA Nephropathy in North American Kidney Transplant Recipients: The Banff Recurrent Glomerulonephritis Working Group Report
Authors: Alachkar Nada , Delsante Marco , Greenberg Ross S. , Koirala Abbal , Alhamad Tarek , Abdalla Basmah , Anand Manish , Boonpheng Ben , Blosser Christopher , Maggiore Umberto , Bagnasco Serena M.
Published: May 2023

Background.

The modified Oxford classification mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents (MEST-C) of immunoglobulin A nephropathy (IgAN) was recently shown to be a predictor of graft failure in Asians with recurrent IgAN. We aimed to validate these findings in a cohort from North American centers participating in the Banff Recurrent Glomerulopathies Working Group.

Methods.

We examined 171 transplant recipients with end-stage kidney disease because of IgAN; 100 of them with biopsy-proven recurrent IgAN (57 of them had complete MEST-C scores) and 71 with no recurrence.

Results.

IgAN recurrence, which was associated with younger age at transplantation (P = 0.012), strongly increased the risk of death-censored graft failure (adjusted hazard ratio, 5.10 [95% confidence interval (CI), 2.26-11.51]; P < 0.001). Higher MEST-C score sum was associated with death-censored graft failure (adjusted hazard ratio, 8.57 [95% CI, 1.23-59.85; P = 0.03] and 61.32 [95% CI, 4.82-779.89; P = 0.002] for score sums 2–3 and 4–5 versus 0, respectively), and so were the single components endocapillary hypercellularity, interstitial fibrosis/tubular atrophy, and crescents (P < 0.05 each). Overall, most of the pooled adjusted hazard ratio estimates associated with each MEST-C component were consistent with those from the Asian cohort (heterogeneity I
2 close to 0%, and P > 0.05).

Conclusions.

Our findings may validate the prognostic usefulness of the Oxford classification for recurrent IgAN and support the inclusion of the MEST-C score in allograft biopsies diagnostic reports.
Novosphingobium mangrovi sp. nov., isolated from mangrove sediment
Authors: Huang Qian , Qian Zhihui , Peng Tao , Li Jin , Ye Xueying , Huang Tongwang , Hu Zhong
Published: May 2023

A novel Gram-stain-negative, aerobic and rod-shaped bacterial strain, designated as HK4-1T, was isolated from mangrove sediments in Hong Kong, PR China. Based on 16S rRNA gene sequence data, strain HK4-1T was found to belong to the genus

Novosphingobium

, family

Erythrobacteraceae

, and showed high similarity to

Novosphingobium chloroacetimidivorans

BUT-14T (96.88 %) and

Novosphingobium indicum

H25T (96.88 %). The G+C content of the whole genome of strain HK4-1T was 64.05 mol%. The major fatty acids were C16 : 0, C18 : 1
 ω7c and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, sphingoglycolipid and two unknown lipids. The predominant respiratory quinone was Q-10. Based on genomic, phylogenetic, phenotypic, physiological and chemotaxonomic data, strain HK4-1T should be classified as representing a novel species of the genus

Novosphingobium

, for which the name Novosphingobium mangrovi sp. nov. is proposed. The type strain of Novosphingobium mangrovi sp. nov. is HK4-1T (=MCCC 1K08252T=JCM 35764T).
Mapping direct and indirect MarA/SoxS/Rob/RamA regulons in Salmonella Typhimurium reveals repression of csgD and biofilm formation
Authors: Middlemiss Alistair D. , Haycocks James R. J. , Stringer Anne M. , Piddock Laura J. V. , Wade Joseph T. , Grainger David C.
Published: May 2023

The closely related transcription factors MarA, SoxS, Rob and RamA control overlapping stress responses in many enteric bacteria. Furthermore, constitutive expression of such regulators is linked to clinical antibiotic resistance. In this work we have mapped the binding of MarA, SoxS, Rob and RamA across the

Salmonella

Typhimurium genome. In parallel, we have monitored changes in transcription start site use resulting from expression of the regulators. Together, these data allow direct and indirect gene regulatory effects to be disentangled. Promoter architecture across the regulon can also be deduced. At a phylogenetic scale, around one third of regulatory targets are conserved in most organisms encoding MarA, SoxS, Rob or RamA. We focused our attention on the control of csgD, which encodes a transcriptional activator responsible for stimulating production of curli fibres during biofilm formation. We show that expression of csgD is particularly sensitive to SoxS that binds upstream to repress transcription. This differs to the situation in

Escherichia coli

, where MarA regulates csgD indirectly.
Risk factor profiles of young women with vasomotor non-obstructive versus obstructive coronary syndromes: Importance of non-traditional and sex-specific risk factors
Authors: Théberge Emilie T. , Vikulova Diana N. , Pimstone Simon N. , Brunham Liam R. , Humphries Karin H. , Sedlak Tara L.
Published: May 2023

Background

Heart disease is the leading cause of premature death for women in Canada. Ischemic heart disease (IHD) is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI CAD). This study aims to study the prevalence of traditional and non-traditional IHD risk factors and their relationships with (M)INOCA compared to MI-CAD and non-MI CAD in young women.

Methods

This study investigated women who presented with premature (≤55 years old) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women’s Heart Health Clinic Registry (WHC) or the Study to Avoid cardioVascular Events in BC (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD or non-MI CAD.

Results

A total of 254 women enrolled between 2015-2022 were analyzed: 77 INOCA and 37 MINOCA from the WHC and 66 with non-MI CAD and 74 MI-CAD from SAVEBC. Regression analyses demonstrated that migraines and preeclampsia/gestational hypertension were the most significant risk factors with higher likelihood to associate with premature (M)INOCA relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood to associate with premature CAD.

Conclusion

There are significant differences in the risk factor profiles of patients with premature (M)INOCA compared to obstructive CAD.
Insights into adipokinetic hormone/corazonin-related peptide receptor specificity and key residues for its activation in the human disease vectorAedes aegyptimosquito
Authors: Afifi Salwa , Paluzzi Jean-Paul
Published: May 2023

Adipokinetic hormone/corazonin-related peptide (ACP) and adipokinetic hormone (AKH) are two neuropeptides that demonstrate homology to the vertebrate gonadotropin-releasing hormone (GnRH). Despite the structural similarity and the close evolutionary relationship between the ACP and the AKH, their signaling systems function independently. To date, the role of ACP and its receptor (ACPR) remains unclear in theAedes aegyptimosquito. Structure-activity relationships (SARs) are often carried out on peptide ligands to determine critical residues for bioactivity and receptor activation; however, residues and features necessary for ligand binding and specificity in the receptors themselves are less studied. Herein, this study focuses on the ACP and AKH signaling systems and examines structural features of their receptors critical for conferring activation and ligand specificity. Firstly, to determine the specific ACPR regions most critical for ligand fidelity and specificity, ACPR chimeras were created by singly replacing each of the three ACPR extracellular loops (ECLs) in their entirety and incorporating the corresponding ECLs from the AKH receptor (AKHR). Heterologous functional assays determined that the three ACPR ECL chimera receptors with complete replacement of full individual ECLs showed no response to either ACP or AKH. These results suggest that the complete replacement of each individual extracellular loop is detrimental to ligand binding and recognition. Secondly, through a more targeted approach, we aimed to determine specific residues critical for functional ligand-binding by substituting only select highly conserved residues within the three ECLs of the ACPR with those from the AKHR. Modifications of specific and highly conserved residues in these ACPR ECLs chimeras suggest that the third extracellular loop contains the most critical residues necessary for ACP binding and receptor activation. In addition, the combination of two selectively-modified ACPR ECLs demonstrated a significant decrease in response to ACP compared to the native ACPR response. Interestingly, combining all of the ACPR ECLs chimeras together resulted in a significant decrease in response to ACP compared to native ACPR. Relatedly, a significantly increased response to AKH was observed in the receptor chimera combining selected modifications in all three ECLs compared to native ACPR. Hence, the particular residues essential for ACP ligand interaction were identified due to the detrimental effect that occurred in ACPR activation after the selective modification of crucial residues localized within the three extracellular domains of the receptor. These data provide key insight into how these two closely related neuropeptidergic systems maintain functional independence in the mosquitoA. aegyptias well as other insects.
External validation of the CAST and rCAST score in patients with out-of-hospital cardiac arrest who underwent ECPR: A secondary analysis of the SAVE-J II study
Authors: Misumi Kayo , Hagiwara Yoshihiro , Kimura Takuya , Hifumi Toru , Inoue Akihiko , Sakamoto Tetsuya , Kuroda Yasuhiro , Ogura Takayuki
Published: May 2023

Background

Risk stratification is important in patients with postcardiac arrest syndrome (PCAS). The post-Cardiac Arrest Syndrome for Therapeutic hypothermia (CAST) and revised CAST (rCAST) scores have been well validated for predicting the accuracy of neurological outcomes, particularly for conventionally resuscitated PCAS patients. However, no studies have evaluated patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).

Methods

Adult patients with out-of-hospital cardiac arrest (OHCA) who underwent ECPR were analyzed in this retrospective observational multicenter cohort study (SAVE-J II study). We validated the accuracy of the CAST and rCAST scores for predicting favorable neurological outcomes (cerebral performance category 1 or 2) at 30 days. Moreover, we compared the predictive performance of these CAST/rCAST scores with those of the previously documented TiPS65 risk model derived from patients with OHCA who were resuscitated using ECPR.

Results

A total of 1135 patients were analyzed. Their median age was 60 years and males comprised 84% of the cohort. The proportion of patients with favorable neurological outcomes was 16.6% overall. In the external validation, the area under the curve (AUC) of the CAST score was numerically larger than those of the rCAST and TiPS65 scores (AUC 0.677 vs. 0.603: p < 0.001, vs. 0.633: p = 0.154, respectively). Both CAST/rCAST risk scores showed good calibration (Hosmer– Lemeshow test: p = 0.726 and 0.674, respectively). Furthermore, the CAST score showed significantly better predictability in net reclassification than did the rCAST (p < 0.001) and TiPS65 scores (p = 0.001).

Conclusions

CAST and rCAST scores can predict neurological outcomes in patients with OHCA who undergo ECPR. The prognostic accuracy of the CAST score was significantly better than that of other pre-existing risk prediction models.

IRB information

The present study was approved by the institutional review board of Kagawa University (approval number: 2018-110)

Clinical trial registration

https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577(unique identifier: UMIN000036490)
Pseudogenes as a neutral reference for detecting selection in prokaryotic pangenomes
Authors: Douglas Gavin M. , Shapiro B. Jesse
Published: May 2023

A long-standing question is to what degree genetic drift and selection drive the divergence in rare accessory gene content between closely related bacteria. Rare genes, including singletons, make up a large proportion of pangenomes (the set of all genes in a set of genomes), but it remains unclear how many such genes are adaptive, deleterious, or neutral to their host genome. Estimates of species’ effective population sizes (Ne) are positively associated with pangenome size and fluidity, which has independently been interpreted as evidence for both neutral and adaptive pangenome models. We hypothesised that pseudogenes, used as a neutral reference, could be used to distinguish these models. We find that most functional categories are depleted for rare pseudogenes when a genome encodes only a single intact copy of a gene family. In contrast, transposons are enriched in pseudogenes, suggesting they are mostly neutral or deleterious to the host genome. Thus, even if individual rare accessory genes vary in their effects on host fitness, we can confidently reject a model of entirely neutral or deleterious rare genes. We also define the ratio of singleton intact genes to singleton pseudogenes (si/sp) within a pangenome, compare this measure across 668 prokaryotic species, and detect a signal consistent with the adaptive value of many rare accessory genes. Taken together, our work demonstrates that comparing to pseudogenes can improve inferences of the evolutionary forces driving pangenome variation.
Examining intra-host genetic variation of RSV by short read high-throughput sequencing
Authors: Henke David , Piedra Felipe-Andrés , Avadhanula Vasanthi , Doddapaneni Harsha , Muzny Donna M. , Menon Vipin K. , Hoffman Kristi L. , Ross Matthew C. , Javornik Cregeen Sara J. , Metcalf Ginger , Gibbs Richard A. , Petrosino Joseph F. , Piedra Pedro A.
Published: May 2023

Every viral infection entails an evolving population of viral genomes. High-throughput sequencing technologies can be used to characterize such populations, but to date there are few published examples of such work. In addition, mixed sequencing data are sometimes used to infer properties of infecting genomes without discriminating between genome-derived reads and reads from the much more abundant, in the case of a typical active viral infection, transcripts. Here we apply capture probe-based short read high-throughput sequencing to nasal wash samples taken from a previously described group of adult hematopoietic cell transplant (HCT) recipients naturally infected with respiratory syncytial virus (RSV). We separately analyzed reads from genomes and transcripts for the levels and distribution of genetic variation by calculating per position Shannon entropies. Our analysis reveals a low level of genetic variation within the RSV infections analyzed here, but with interesting differences between genomes and transcripts in 1) average per sample Shannon entropies; 2) the genomic distribution of variation ‘hotspots’; and 3) the genomic distribution of hotspots encoding alternative amino acids. In all, our results suggest the importance of separately analyzing reads from genomes and transcripts when interpreting high-throughput sequencing data for insight into intra-host viral genome replication, expression, and evolution.
PenTag, a Versatile Platform for Synthesizing Protein-Polymer Biohybrid Materials
Authors: Mohsenin Hasti , Pacheco Jennifer , Kemmer Svenja , Wagner Hanna J. , Höfflin Nico , Bergmann Toquinha , Baumann Tim , Jerez-Longres Carolina , Ripp Alexander , Jork Nikolaus , Jessen Henning J. , Fussenegger Martin , Köhn Maja , Timmer Jens , Weber Wilfried
Published: May 2023

The site-specific and covalent conjugation of proteins on solid supports and in hydrogels is the basis for the synthesis of biohybrid materials offering broad applications. Current methods for conjugating proteins to desired targets are often challenging due to unspecific binding, unstable (non-covalent) coupling, or expensive and difficult-to-synthesize ligand molecules. Here, we present PenTag, an approach for the biorthogonal, highly-specific and covalent conjugation of a protein to its ligand for various applications in materials sciences. We engineered penicillin- binding protein 3 (PBP3) and showed that this protein can be used for the stable and spontaneous conjugation of proteins to dyes, polymers, or solid supports. We applied PenTag as a crosslinking tool for synthesizing stimuli-responsive hydrogels or for the development of a biohybrid material system performing computational operations emulating a 4:2 encoder. Based on this broad applicability and the use of a small, cheap and easy-to-functionalize ligand and a stable, soluble recombinant protein, we see PenTag as a versatile approach towards biohybrid material synthesis.
Neural representations of economic decision variables in human posterior parietal cortex
Authors: Klaes Christian , Pilacinski Artur , Kellis Spencer , Aflalo Tyson , Liu Charles , Andersen Richard
Published: May 2023

Decision making has been intensively studied in the posterior parietal cortex in non-human primates on a single neuron level. In humans decision making has mainly been studied with psychophysical tools or with fMRI. Here, we investigated how single neurons from human posterior parietal cortex represent numeric values informing future decisions during a complex two-player game. The tetraplegic study participant was implanted with a Utah electrode array in the anterior intraparietal area (AIP). We played a simplified variant of Black Jack with the participant while neuronal data was recorded. During the game two players are presented with numbers which are added up. Each time a number is presented the player has to decide to proceed or to stop. Once the first player stops or the score reaches a limit the turn passes on to the second player who tries to beat the score of the first player. Whoever is closer to the limit (without overshooting) wins the game. We found that many AIP neurons selectively responded to the face value of the presented number. Other neurons tracked the cumulative score or were selectively active for the upcoming decision of the study participant. Interestingly, some cells also kept track of the opponent’s score. Our findings show that parietal regions engaged in hand action control also represent numbers and their complex transformations. This is also the first demonstration of complex economic decisions being possible to track in single neuron activity in human AIP. Our findings show how tight are the links between parietal neural circuits underlying hand control, numerical cognition and complex decision-making.